Inflammation in diabetic nephropathy

Andy K H Lim, Gregory H Tesch, Andy K H Lim, Gregory H Tesch

Abstract

Diabetic nephropathy is the leading cause of end-stage kidney disease worldwide but current treatments remain suboptimal. This review examines the evidence for inflammation in the development and progression of diabetic nephropathy in both experimental and human diabetes, and provides an update on recent novel experimental approaches targeting inflammation and the lessons we have learned from these approaches. We highlight the important role of inflammatory cells in the kidney, particularly infiltrating macrophages, T-lymphocytes and the subpopulation of regulatory T cells. The possible link between immune deposition and diabetic nephropathy is explored, along with the recently described immune complexes of anti-oxidized low-density lipoproteins. We also briefly discuss some of the major inflammatory cytokines involved in the pathogenesis of diabetic nephropathy, including the role of adipokines. Lastly, we present the latest data on the pathogenic role of the stress-activated protein kinases in diabetic nephropathy, from studies on the p38 mitogen activated protein kinase and the c-Jun amino terminal kinase cell signalling pathways. The genetic and pharmacological approaches which reduce inflammation in diabetic nephropathy have not only enhanced our understanding of the pathophysiology of the disease but shown promise as potential therapeutic strategies.

Figures

Figure 1
Figure 1
The inflammatory amplification loop in the diabetic kidney. Circulating immune cells such as monocytes are recruited into the diabetic kidney due to upregulation of adhesion molecules such as ICAM-1. Chemokines such as MCP-1 act as chemoattractants which promote accumulation of the immune cells in the kidney. These immune cells are activated by numerous signals such as the ligation of c-fms by CSF-1, receptor for AGE by AGEs, and the Fcγ receptors by antioxidized LDL immune complexes. CSF-1 also promotes the maturation, proliferation, and survival of monocyte-macrophages. Activated immune cells act as inflammatory cells and elaborate proinflammatory cytokines and reactive oxygen species (ROS), which trigger a cell signalling cascade mediated by the stress-activated protein kinases, p38 MAPK, and JNK. These kidney cells then respond by the production of chemokines such as MCP-1 and CSF-1, and profibrotic factors such as TGF-β which increase extracellular matrix production by mesangial cells and interstitial fibroblasts. Ultimately, there is cellular injury and progressive fibrosis within the diabetic kidney.

References

    1. Galkina E, Ley K. Leukocyte recruitment and vascular injury in diabetic nephropathy. Journal of the American Society of Nephrology. 2006;17(2):368–377.
    1. Chow F, Ozols E, Nikolic-Paterson DJ, Atkins RC, Tesch GH. Macrophages in mouse type 2 diabetic nephropathy: correlation with diabetic state and progressive renal injury. Kidney International. 2004;65(1):116–128.
    1. Chow FY, Nikolic-Paterson DJ, Atkins RC, Tesch GH. Macrophages in streptozotocin-induced diabetic nephropathy: potential role in renal fibrosis. Nephrology Dialysis Transplantation. 2004;19(12):2987–2996.
    1. Furuta T, Saito T, Ootaka T, et al. The role of macrophages in diabetic glomerulosclerosis. American Journal of Kidney Diseases. 1993;21(5):480–485.
    1. Nguyen D, Ping F, Mu W, Hill P, Atkins RC, Chadban SJ. Macrophage accumulation in human progressive diabetic nephropathy. Nephrology. 2006;11(3):226–231.
    1. Chow FY, Nikolic-Paterson DJ, Ozols E, Atkins RC, Tesch GH. Intercellular adhesion molecule-1 deficiency is protective against nephropathy in type 2 diabetic db/db mice. Journal of the American Society of Nephrology. 2005;16(6):1711–1722.
    1. Morii T, Fujita H, Narita T, et al. Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy. Journal of Diabetes and its Complications. 2003;17(1):11–15.
    1. Kanamori H, Matsubara T, Mima A, et al. Inhibition of MCP-1/CCR2 pathway ameliorates the development of diabetic nephropathy. Biochemical and Biophysical Research Communications. 2007;360(4):772–777.
    1. Chow FY, Nikolic-Paterson DJ, Ma FY, Ozols E, Rollins BJ, Tesch GH. Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice. Diabetologia. 2007;50(2):471–480.
    1. Chow FY, Nikolic-Paterson DJ, Ozols E, Atkins RC, Rollin BJ, Tesch GH. Monocyte chemoattractant protein-1 promotes the development of diabetic renal injury in streptozotocin-treated mice. Kidney International. 2006;69(1):73–80.
    1. Lim AKH, Ma FY, Nikolic-Paterson DJ, Thomas MC, Hurst LA, Tesch GH. Antibody blockade of c-fms suppresses the progression of inflammation and injury in early diabetic nephropathy in obese db/db mice. Diabetologia. 2009;52(8):1669–1679.
    1. Tipping PG, Holdsworth SR. T cells in crescentic glomerulonephritis. Journal of the American Society of Nephrology. 2006;17(5):1253–1263.
    1. Xiao X, Ma B, Dong B, et al. Cellular and humoral immune responses in the early stages of diabetic nephropathy in NOD mice. Journal of Autoimmunity. 2009;32(2):85–93.
    1. Moriya R, Manivel JC, Mauer M. Juxtaglomerular apparatus T-cell infiltration affects glomerular structure in Type 1 diabetic patients. Diabetologia. 2004;47(1):82–88.
    1. Odobasic D, Kitching AR, Semple TJ, Timoshanko JR, Tipping PG, Holdsworth SR. Glomerular expression of CD80 and CD86 is required for leukocyte accumulation and injury in crescentic glomerulonephritis. Journal of the American Society of Nephrology. 2005;16(7):2012–2022.
    1. Imani F, Horii Y, Suthanthiran M, et al. Advanced glycosylation endproduct-specific receptors on human and rat T- lymphocytes mediate synthesis of interferon γ: role in tissue remodeling. Journal of Experimental Medicine. 1993;178(6):2165–2172.
    1. LeBleu VS, Sugimoto H, Miller CA, Gattone VH, Kalluri R. Lymphocytes are dispensable for glomerulonephritis but required for renal interstitial fibrosis in matrix defect-induced Alport renal disease. Laboratory Investigation. 2008;88(3):284–292.
    1. Kinsey GR, Sharma R, Huang L, et al. Regulatory T cells suppress innate immunity in kidney ischemia-reperfusion injury. Journal of the American Society of Nephrology. 2009;20(8):1744–1753.
    1. Lim AKH, Ma FY, Nikolic-Paterson DJ, Kitching AR, Thomas MC, Tesch GH. Lymphocytes promote albuminuria, but not renal dysfunction or histological damage in a mouse model of diabetic renal injury. Diabetologia. 2010;53(8):1772–1782.
    1. Zhen Y, Sun L, Liu H, et al. Alterations of peripheral CD4 + CD25 + Foxp3 + T regulatory cells in mice with STZ-induced diabetes. Cellular and Molecular Immunology. 2012;9(1):75–85.
    1. Eller K, Kirsch A, Wolf AM, et al. Potential role of regulatory T cells in reversing obesity-linked insulin resistance and diabetic nephropathy. Diabetes. 2011;60(11):2954–2962.
    1. Mironova M, Virella G, Lopes-Virella MF. Isolation and characterization of human antioxidized LDL autoantibodies. Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16(2):222–229.
    1. Lopes-Virella MF, Virella G. The role of immune and inflammatory processes in the development of macrovascular disease in diabetes. Frontiers in Bioscience. 2003;8:s750–s768.
    1. Atchley D, Lopes-Virella M, Zheng D, Kenny D, Virella G. Oxidized LDL-anti-oxidized LDL immune complexes and diabetic nephropathy. Diabetologia. 2002;45(11):1562–1571.
    1. Virella G, Carter RE, Saad A, Crosswell EG, Game BA, Lopes-Virella MF. Distribution of IgM and IgG antibodies to oxidized LDL in immune complexes isolated from patients with type 1 diabetes and its relationship with nephropathy. Clinical Immunology. 2008;127(3):394–400.
    1. Hora K, Satriano JA, Santiago A, et al. Receptors for IgG complexes activate synthesis of monocyte chemoattractant peptide 1 and colony-stimulating factor 1. Proceedings of the National Academy of Sciences of the United States of America. 1992;89(5):1745–1749.
    1. Abdelsamie SA, Li Y, Huang Y, et al. Oxidized LDL immune complexes stimulate collagen IV production in mesangial cells via Fc gamma receptors I and III. Clinical Immunology. 2011;139(3):258–266.
    1. Saad AF, Virella G, Chassereau C, Boackle RJ, Lopes-Virella MF. OxLDL immune complexes activate complement and induce cytokine production by MonoMac 6 cells and human macrophages. Journal of Lipid Research. 2006;47(9):1975–1983.
    1. Abrass CK. Evaluation of the presence of circulating immune complexes and their relationship to glomerular IgG deposits in streptozotocin-induced diabetic rats. Clinical and Experimental Immunology. 1984;57(1):17–24.
    1. Ainsworth SK, Hirsch HZ, Brackett NC. Diabetic glomerulonephropathy: histopathologic, immunofluorescent, and ultrastructural studies of 16 cases. Human Pathology. 1982;13(5):470–478.
    1. Haider DG, Peric S, Friedl A, et al. Kidney biopsy in patients with diabetes mellitus. Clinical Nephrology. 2011;76(3):180–185.
    1. Brosius FC, Alpers CE, Bottinger EP, et al. Mouse models of diabetic nephropathy. Journal of the American Society of Nephrology. 2009;20(12):2503–2512.
    1. Wu C-C, Sytwu H-K, Lin Y-F. Cytokines in diabetic nephropathy. Advances in Clinical Chemistry. 2012;56:55–74.
    1. Chiarelli F, Gaspari S, Marcovecchio ML. Role of growth factors in diabetic kidney disease. Hormone and Metabolic Research. 2009;41(8):585–593.
    1. Jevnikar AM, Brennan DC, Singer GG, et al. Stimulated kidney tubular epithelial cells express membrane associated and secreted TNFα . Kidney International. 1991;40(2):203–211.
    1. Nakamura T, Fukui M, Ebihara I, et al. mRNA expression of growth factors in glomeruli from diabetic rats. Diabetes. 1993;42(3):450–456.
    1. Sugimoto H, Shikata K, Wada J, Horiuchi S, Makino H. Advanced glycation end products-cytokine-nitric oxide sequence pathway in the development of diabetic nephropathy: aminoguanidine ameliorates the overexpression of tumour necrosis factor-α and inducible nitric oxide synthase in diabetic rat glomeruli. Diabetologia. 1999;42(7):878–886.
    1. Dong X, Swaminathan S, Bachman LA, Croatt AJ, Nath KA, Griffin MD. Resident dendritic cells are the predominant TNF-secreting cell in early renal ischemia-reperfusion injury. Kidney International. 2007;71(7):619–628.
    1. Mensah-Brown EPK, Obineche EN, Galadari S, et al. Streptozotocin-induced diabetic nephropathy in rats: the role of inflammatory cytokines. Cytokine. 2005;31(3):180–190.
    1. Radeke HH, Meier B, Topley N, Floge J, Habermehl GG, Resch K. Interleukin 1-α and tumor necrosis factor-α induce oxygen radical production in mesangial cells. Kidney International. 1990;37(2):767–775.
    1. Koike N, Takamura T, Kaneko S. Induction of reactive oxygen species from isolated rat glomeruli by protein kinase C activation and TNF-α stimulation, and effects of a phosphodiesterase inhibitor. Life Sciences. 2007;80(18):1721–1728.
    1. Mccarthy ET, Sharma R, Sharma M, et al. TNF-α increases albumin permeability of isolated rat glomeruli through the generation of superoxide. Journal of the American Society of Nephrology. 1998;9(3):433–438.
    1. Laster SM, Wood JG, Gooding LR. Tumor necrosis factor can induce both apoptic and necrotic forms of cell lysis. Journal of Immunology. 1988;141(8):2629–2634.
    1. Boyle JJ, Weissberg PL, Bennett MR. Tumor necrosis factor-α promotes macrophage-induced vascular smooth muscle cell apoptosis by direct and autocrine mechanisms. Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23(9):1553–1558.
    1. Baud L, Ardaillou R. Tumor necrosis factor in renal injury. Mineral and Electrolyte Metabolism. 1995;21(4-5):336–341.
    1. Gomez-Chiarri M, Ortiz A, Lerma JL, et al. Involvement of tumor necrosis factor and platelet-activating factor in the pathogenesis of experimental nephrosis in rats. Laboratory Investigation. 1994;70(4):449–459.
    1. Marsden PA, Brenner BM. Transcriptional regulation of the endothelin-1 gene by TNF-α . American Journal of Physiology, Cell Physiology. 1992;262(4):C854–C861.
    1. Marsden PA, Ballermann BJ. Tumor necrosis factor α activates soluble guanylate cyclase in bovine glomerular mesangial cells via an L-arginine-dependent mechanism. Journal of Experimental Medicine. 1990;172(6):1843–1852.
    1. Wójciak-Stothard B, Entwistle A, Garg R, Ridley AJ. Regulation of TNF-α-induced reorganization of the actin cytoskeleton and cell-cell junctions by Rho, Rac, and Cdc42 in human endothelial cells. Journal of Cellular Physiology. 1998;176(1):150–165.
    1. Moriwaki Y, Yamamoto T, Shibutani Y, et al. Elevated levels of interleukin-18 and tumor necrosis factor-α in serum of patients with type 2 diabetes mellitus: relationship with diabetic nephropathy. Metabolism: Clinical and Experimental. 2003;52(5):605–608.
    1. Navarro JF, Mora C, Macía M, García J. Inflammatory parameters are independently associated with urinary albumin in type 2 diabetes mellitus. American Journal of Kidney Diseases. 2003;42(1):53–61.
    1. Navarro JF, Mora C, Muros M, García J. Urinary tumour necrosis factor-α excretion independently correlates with clinical markers of glomerular and tubulointerstitial injury in type 2 diabetic patients. Nephrology Dialysis Transplantation. 2006;21(12):3428–3434.
    1. Gu L, Tseng SC, Rollins BJ. Monocyte chemoattractant protein-1. Chemical Immunology. 1999;72:7–29.
    1. Viedt C, Orth SR. Monocyte chemoattractant protein-1 (MCP-1) in the kidney: does it more than simply attract monocytes? Nephrology Dialysis Transplantation. 2002;17(12):2043–2047.
    1. Kato S, Luyckx VA, Ots M, et al. Renin-angiotensin blockade lowers MCP-1 expression in diabetic rats. Kidney International. 1999;56(3):1037–1048.
    1. Gruden G, Setti G, Hayward A, et al. Mechanical stretch induces monocyte chemoattractant activity via an NF-κB-dependent monocyte chemoattractant protein-1-mediated pathway in human mesangial cells: inhibition by rosiglitazone. Journal of the American Society of Nephrology. 2005;16(3):688–696.
    1. Amann B, Tinzmann R, Angelkort B. ACE inhibitors improve diabetic nephropathy through suppression of renal MCP-1. Diabetes Care. 2003;26(8):2421–2425.
    1. Han SY, Kim CH, Kim HS, et al. Spironolactone prevents diabetic nephropathy through an anti-inflammatory mechanism in type 2 diabetic rats. Journal of the American Society of Nephrology. 2006;17(5):1362–1372.
    1. Sugimoto H, Shikata K, Hirata K, et al. Increased expression of intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli: glomerular hyperfiltration is a potential mechanism of ICAM-1 upregulation. Diabetes. 1997;46(12):2075–2081.
    1. Matsui H, Suzuki M, Tsukuda R, Iida K, Miyasaka M, Ikeda H. Expression of ICAM-1 on glomeruli is associated with progression of diabetic nephropathy in a genetically obese diabetic rat, Wistar fatty. Diabetes Research and Clinical Practice. 1996;32(1-2):1–9.
    1. Okada S, Shikata K, Matsuda M, et al. Intercellular adhesion molecule-1-deficient mice are resistant against renal injury after induction of diabetes. Diabetes. 2003;52(10):2586–2593.
    1. Güler S, Cakir B, Demirbas B, et al. Plasma soluble intercellular adhesion molecule 1 levels are increased in type 2 diabetic patients with nephropathy. Hormone Research. 2002;58(2):67–70.
    1. Seron D, Cameron JS, Haskard DO. Expression of VCAM-1 in the normal and diseased kidney. Nephrology Dialysis Transplantation. 1991;6(12):917–922.
    1. Ina K, Kitamura H, Okeda T, et al. Vascular cell adhesion molecule-1 expression in the renal interstitium of diabetic KKAy mice. Diabetes Research and Clinical Practice. 1999;44(1):1–8.
    1. Wang F, Li M, Cheng L, et al. Intervention with cilostazol attenuates renal inflammation in streptozotocin-induced diabetic rats. Life Sciences. 2008;83(25-26):828–835.
    1. Clausen P, Jacobsen P, Rossing K, Jensen JS, Parving HH, Feldt-Rasmussen B. Plasma concentrations of VCAM-1 and ICAM-1 are elevated in patients with Type 1 diabetes mellitus with microalbuminuria and overt nephropathy. Diabetic Medicine. 2000;17(9):644–649.
    1. Rubio-Guerra AF, Vargas-Robles H, Lozano Nuevo JJ, Escalante-Acosta BA. Correlation between circulating adhesion molecule levels and albuminuria in type-2 diabetic hypertensive patients. Kidney and Blood Pressure Research. 2009;32(2):106–109.
    1. Navarro JF, Milena FJ, Mora C, León C, García J. Renal pro-inflammatory cytokine gene expression in diabetic nephropathy: effect of angiotensin-converting enzyme inhibition and pentoxifylline administration. American Journal of Nephrology. 2007;26(6):562–570.
    1. Sassy-Prigent C, Heudes D, Mandet C, et al. Early glomerular macrophage recruitment in streptozotocin-induced diabetic rats. Diabetes. 2000;49(3):466–475.
    1. Brady HR. Leukocyte adhesion molecules and kidney diseases. Kidney International. 1994;45(5):1285–1300.
    1. Park CW, Kim JH, Lee JW, et al. High glucose-induced intercellular adhesion molecule-1 (ICAM-1) expression through an osmotic effect in rat mesangial cells is PKC-NF-κB-dependent. Diabetologia. 2000;43(12):1544–1553.
    1. Pfeilschifter J, Pignat W, Vosbeck K, Marki F. Interleukin 1 and tumor necrosis factor synergistically stimulate prostaglandin synthesis and phospholipase A2 release from rat renal mesangial cells. Biochemical and Biophysical Research Communications. 1989;159(2):385–394.
    1. Royall JA, Berkow RL, Beckman JS, Cunningham MK, Matalon S, Freeman BA. Tumor necrosis factor and interleukin 1α increase vascular endothelial permeability. American Journal of Physiology, Lung Cellular and Molecular Physiology. 1989;257(6):L399–L410.
    1. Vesey DA, Cheung C, Cuttle L, Endre Z, Gobe G, Johnson DW. Interleukin-1 β stimulates human renal fibroblast proliferation and matrix protein production by means of a transforming growth factor-β-dependent mechanism. Journal of Laboratory and Clinical Medicine. 2002;140(5):342–350.
    1. Lee SH, Ihm CG, Sohn SD, et al. Polymorphisms in interleukin-1β and interleukin-1 receptor antagonist genes are associated with kidney failure in Korean patients with type 2 diabetes mellitus. American Journal of Nephrology. 2004;24(4):410–414.
    1. Tarnow L, Pociot F, Hansen PM, et al. Polymorphisms in the interleukin-1 gene cluster do not contribute to the genetic susceptibility of diabetic nephropathy in Caucasian patients with IDDM. Diabetes. 1997;46(6):1075–1076.
    1. Thomson SC, Deng A, Bao D, Satriano J, Blantz RC, Vallon V. Ornithine decarboxylase, kidney size, and the tubular hypothesis of glomerular hyperfiltration in experimental diabetes. Journal of Clinical Investigation. 2001;107(2):217–224.
    1. Coleman DL, Ruef C. Interleukin-6: an autocrine regulator of mesangial cell growth. Kidney International. 1992;41(3):604–606.
    1. Suzuki D, Miyazaki M, Naka R, et al. In situ hybridization of interleukin 6 in diabetic nephropathy. Diabetes. 1995;44(10):1233–1238.
    1. Hirano T, Akira S, Taga T, Kishimoto T. Biological and clinical aspects of interleukin 6. Immunology Today. 1990;11(12):443–449.
    1. Ruef C, Budde K, Lacy J, et al. Interleukin 6 is an autocrine growth factor for mesangial cells. Kidney International. 1990;38(2):249–257.
    1. Aso Y, Yoshida N, Okumura KI, et al. Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia. Clinica Chimica Acta. 2004;348(1-2):139–145.
    1. Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH. Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients. Diabetologia. 2003;46(10):1402–1407.
    1. Dalla Vestra M, Mussap M, Gallina P, et al. Acute-phase markers of inflammation and glomerular structure in patients with type 2 diabetes. Journal of the American Society of Nephrology. 2005;16(3) supplement 1:S78–S82.
    1. Okamura H, Tsutsui H, Komatsu T, et al. Cloning of a new cytokine that induces IFN-γ production by T cells. Nature. 1995;378(6552):88–91.
    1. Dai SM, Matsuno H, Nakamura H, Nishioka K, Yudoh K. Interleukin-18 enhances monocyte tumor necrosis factor α and interleukin-1β production induced by direct contact with T lymphocytes: implications in rheumatoid arthritis. Arthritis and Rheumatism. 2004;50(2):432–443.
    1. Mariño E, Cardier JE. Differential effect of IL-18 on endothelial cell apoptosis mediated by TNF-α and Fas (CD95) Cytokine. 2003;22(5):142–148.
    1. Stuyt RJL, Netea MG, Geijtenbeek TBH, Kullberg BJ, Dinarello CA, Van Der Meer JWM. Selective regulation of intercellular adhesion molecule-1 expression by interleukin-18 and interleukin-12 on human monocytes. Immunology. 2003;110(3):329–334.
    1. Melnikov VY, Ecder T, Fantuzzi G, et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. Journal of Clinical Investigation. 2001;107(9):1145–1152.
    1. Melnikov VY, Faubel S, Siegmund B, Scott Lucia M, Ljubanovic D, Edelstein CL. Neutrophil-independent mechanisms of caspase-1- and IL-18-mediated ischemic acute tubular necrosis in mice. Journal of Clinical Investigation. 2002;110(8):1083–1091.
    1. Nakamura A, Shikata K, Hiramatsu M, et al. Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes. Diabetes Care. 2005;28(12):2890–2895.
    1. Ouedraogo R, Gong Y, Berzins B, et al. Adiponectin deficiency increases leukocyte-endothelium interactions via upregulation of endothelial cell adhesion molecules in vivo. Journal of Clinical Investigation. 2007;117(6):1718–1726.
    1. Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000;96(5):1723–1732.
    1. Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation. 2001;103(8):1057–1063.
    1. Wang Y, Lam KSL, Xu JY, et al. Adiponectin inhibits cell proliferation by interacting with several growth factors in an oligomerization-dependent manner. Journal of Biological Chemistry. 2005;280(18):18341–18347.
    1. Tamura Y, Murayama T, Minami M, Matsubara T, Yokode M, Arai H. Ezetimibe ameliorates early diabetic nephropathy in db/db mice. Journal of Atherosclerosis and Thrombosis. 2012;19(7):608–618.
    1. Nakamaki S, Satoh H, Kudoh A, Hayashi Y, Hirai H, Watanabe T. Adiponectin reduces proteinuria in streptozotocin-induced diabetic wistar rats. Experimental Biology and Medicine. 2011;236(5):614–620.
    1. Schalkwijk CG, Chaturvedi N, Schram MT, Fuller JH, Stehouwer CDA. Adiponectin is inversely associated with renal function in type 1 diabetic patients. Journal of Clinical Endocrinology and Metabolism. 2006;91(1):129–135.
    1. Saraheimo M, Forsblom C, Fagerudd J, et al. Serum adiponectin is increased in type 1 diabetic patients with nephropathy. Diabetes Care. 2005;28(6):1410–1414.
    1. Kato K, Osawa H, Ochi M, et al. Serum total and high molecular weight adiponectin levels are correlated with the severity of diabetic retinopathy and nephropathy. Clinical Endocrinology. 2008;68(3):442–449.
    1. Rivero A, Mora C, Muros M, García J, Herrera H, Navarro-González JF. Pathogenic perspectives for the role of inflammation in diabetic nephropathy. Clinical Science. 2009;116(6):479–492.
    1. Hanai KO, Babazono T, Mugishima M, et al. Association of serum leptin levels with progression of diabetic kidney disease in patients with type 2 diabetes. Diabetes Care. 2011;34(12):2557–2559.
    1. Fruehwald-Schultes B, Kern W, Beyer J, Forst T, Pfützner A, Peters A. Elevated serum leptin concentrations in type 2 diabetic patients with microalbuminuria and macroalbuminuria. Metabolism: Clinical and Experimental. 1999;48(10):1290–1293.
    1. Axelsson J, Bergsten A, Qureshi AR, et al. Elevated resistin levels in chronic kidney disease are associated with decreased glomerular filtration rate and inflammation, but not with insulin resistance. Kidney International. 2006;69(3):596–604.
    1. Ma FY, Liu J, Nikolic-Paterson DJ. The role of stress-activated protein kinase signaling in renal pathophysiology. Brazilian Journal of Medical and Biological Research. 2009;42(1):29–37.
    1. Adhikary L, Chow F, Nikolic-Paterson DJ, et al. Abnormal p38 mitogen-activated protein kinase signalling in human and experimental diabetic nephropathy. Diabetologia. 2004;47(7):1210–1222.
    1. Sakai N, Wada T, Furuichi K, et al. Involvement of extracellular signal-regulated kinase and p38 in human diabetic nephropathy. American Journal of Kidney Diseases. 2005;45(1):54–65.
    1. Stambe C, Atkins RC, Tesch GH, et al. Blockade of p38α MAPK ameliorates acute inflammatory renal injury in rat anti-GBM glomerulonephritis. Journal of the American Society of Nephrology. 2003;14(2):338–351.
    1. Stambe C, Atkins RC, Tesch GH, Masaki T, Schreiner GF, Nikolic-Paterson DJ. The Role of p38α mitogen-activated protein kinase activation in renal fibrosis. Journal of the American Society of Nephrology. 2004;15(2):370–379.
    1. Wilmer WA, Dixon CL, Hebert C. Chronic exposure of human mesangial cells to high glucose environments activates the p38 MAPK pathway. Kidney International. 2001;60(3):858–871.
    1. Susztak K, Raff AC, Schiffer M, Böttinger EP. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes. 2006;55(1):225–233.
    1. Zhang SL, Tang SS, Chen X, Filep JG, Ingelfinger JR, Chan JSD. High levels of glucose stimulate angiotensinogen gene expression via the p38 mitogen-activated protein kinase pathway in rat kidney proximal tubular cells. Endocrinology. 2000;141(12):4637–4646.
    1. Daoud S, Schinzel R, Neumann A, et al. Advanced glycation endproducts: activators of cardiac remodeling in primary fibroblasts from adult rat hearts. Molecular Medicine. 2001;7(8):543–551.
    1. Liu BF, Miyata S, Hirota Y, et al. Methylglyoxal induces apoptosis through activation of p38 mitogen-activated protein kinase in rat mesangial cells. Kidney International. 2003;63(3):947–957.
    1. Kang YS, Park YG, Kim BK, et al. Angiotensin II stimulates the synthesis of vascular endothelial growth factor through the p38 mitogen activated protein kinase pathway in cultured mouse podocytes. Journal of Molecular Endocrinology. 2006;36(2):377–388.
    1. Chuang PY, Yu Q, Fang W, Uribarri J, He JC. Advanced glycation endproducts induce podocyte apoptosis by activation of the FOXO4 transcription factor. Kidney International. 2007;72(8):965–976.
    1. Porras A, Zuluaga S, Black E, et al. p38α Mitogen-activated Protein Kinase Sensitizes Cells to Apoptosis Induced by Different Stimuli. Molecular Biology of the Cell. 2004;15(2):922–933.
    1. Takaishi H, Taniguchi T, Takahashi A, Ishikawa Y, Yokoyama M. High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells. Biochemical and Biophysical Research Communications. 2003;305(1):122–128.
    1. Suzuki H, Uchida K, Nitta K, Nihei H. Role of mitogen-activated protein kinase in the regulation of transforming growth factor-β-induced fibronectin accumulation in cultured renal interstitial fibroblasts. Clinical and Experimental Nephrology. 2004;8(3):188–195.
    1. Chin BY, Mohsenin A, Li SX, Choi AMK, Choi ME. Stimulation of pro-α1(I) collagen by TGF-β1 in mesangial cells: role of the p38 MAPK pathway. American Journal of Physiology. 2001;280(3):F495–F504.
    1. Fujita H, Omori S, Ishikura K, Hida M, Awazu M. ERK and p38 mediate high-glucose-induced hypertrophy and TGF-β expression in renal tubular cells. American Journal of Physiology. 2004;286(1):F120–F126.
    1. Wu DT, Bitzer M, Ju W, Mundel P, Böttinger EP. TGF-β concentration specifies differential signaling profiles of growth arrest/differentiation and apoptosis in podocytes. Journal of the American Society of Nephrology. 2005;16(11):3211–3221.
    1. Schiffer M, Bitzer M, Roberts ISD, et al. Apoptosis in podocytes induced by TGF-β and Smad7. Journal of Clinical Investigation. 2001;108(6):807–816.
    1. Zhuang S, Yan Y, Han J, Schnellmann RG. p38 kinase-mediated transactivation of the epidermal growth factor receptor is required for dedifferentiation of renal epithelial cells after oxidant injury. Journal of Biological Chemistry. 2005;280(22):21036–21042.
    1. Jung DS, Li JJ, Kwak SJ, et al. FR167653 inhibits fibronectin expression and apoptosis in diabetic glomeruli and in high-glucose-stimulated mesangial cells. American Journal of Physiology. 2008;295(2):F595–F604.
    1. Wang L, Ma R, Flavell RA, Choi ME. Requirement of mitogen-activated protein kinase kinase 3 (MKK3) for activation of p38α and p38δ MAPK isoforms by TGF-β1 in murine mesangial cells. Journal of Biological Chemistry. 2002;277(49):47257–47262.
    1. Wang L, Kwak JH, Kim SI, He Y, Choi ME. Transforming growth factor-β1 stimulates vascular endothelial growth factor 164 via mitogen-activated protein kinase kinase 3-p38α and p38δ mitogen-activated protein kinase-dependent pathway in murine mesangial cells. Journal of Biological Chemistry. 2004;279(32):33213–33219.
    1. Lim AKH, Nikolic-Paterson DJ, Ma FY, et al. Role of MKK3-p38 MAPK signalling in the development of type 2 diabetes and renal injury in obese db/db mice. Diabetologia. 2009;52(2):347–358.
    1. Bogoyevitch MA, Boehm I, Oakley A, Ketterman AJ, Barr RK. Targeting the JNK MAPK cascade for inhibition: basic science and therapeutic potential. Biochimica et Biophysica Acta. 2004;1697(1-2):89–101.
    1. Wang L, Matsushita K, Araki I, Takeda M. Inhibition of c-Jun N-terminal kinase ameliorates apoptosis induced by hydrogen peroxide in the kidney tubule epithelial cells (NRK-52E) Nephron. 2002;91(1):142–147.
    1. Pulverer BJ, Kyriakis JM, Avruch J, Nikolakaki E, Woodgett JR. Phosphorylation of c-jun mediated by MAP kinases. Nature. 1991;353(6345):670–674.
    1. Ip YT, Davis RJ. Signal transduction by the c-Jun N-terminal kinase (JNK)—from inflammation to development. Current Opinion in Cell Biology. 1998;10(2):205–219.
    1. Himes SR, Sester DP, Ravasi T, Cronau SL, Sasmono T, Hume DA. The JNK are important for development and survival of macrophages. Journal of Immunology. 2006;176(4):2219–2228.
    1. Mao C, Ray-Gallet D, Tavitian A, Moreau-Gachelin F. Differential phosphorylations of Spi-B and Spi-1 transcription factors. Oncogene. 1996;12(4):863–873.
    1. Flanc RS, Ma FY, Tesch GH, et al. A pathogenic role for JNK signaling in experimental anti-GBM glomerulonephritis. Kidney International. 2007;72(6):698–708.
    1. Ma FY, Flanc RS, Tesch GH, et al. A pathogenic role for c-Jun amino-terminal kinase signaling in renal fibrosis and tubular cell apoptosis. Journal of the American Society of Nephrology. 2007;18(2):472–484.
    1. De Borst MH, Prakash J, Sandovici M, et al. c-Jun NH2-terminal kinase is crucially involved in renal tubulo-interstitial inflammation. Journal of Pharmacology and Experimental Therapeutics. 2009;331(3):896–905.
    1. De Borst MH, Prakash J, Melenhorst WBWH, et al. Glomerular and tubular induction of the transcription factor c-Jun in human renal disease. Journal of Pathology. 2007;213(2):219–228.
    1. Lim AKH, Ma FY, Nikolic-Paterson DJ, et al. Evaluation of JNK blockade as an early intervention treatment for type 1 diabetic nephropathy in hypertensive rats. American Journal of Nephrology. 2011;34(4):337–346.
    1. Ijaz A, Tejada T, Catanuto P, et al. Inhibition of C-jun N-terminal kinase improves insulin sensitivity but worsens albuminuria in experimental diabetes. Kidney International. 2009;75(4):381–388.
    1. Mohan S, Reddick RL, Musi N, et al. Diabetic eNOS knockout mice develop distinct macro- and microvascular complications. Laboratory Investigation. 2008;88(5):515–528.
    1. Sato W, Kosugi T, Zhang L, et al. The pivotal role of VEGF on glomerular macrophage infiltration in advanced diabetic nephropathy. Laboratory Investigation. 2008;88(9):949–961.
    1. Lassila M, Seah KK, Allen TJ, et al. Accelerated nephropathy in diabetic apolipoprotein E-knockout mouse: role of advanced glycation end products. Journal of the American Society of Nephrology. 2004;15(8):2125–2138.
    1. Kikuchi Y, Imakiire T, Yamada M, et al. Mizoribine reduces renal injury and macrophage infiltration in non-insulin-dependent diabetic rats. Nephrology Dialysis Transplantation. 2005;20(8):1573–1581.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren