The Expression of AQP5 and UTs in the Sweat Glands of Uremic Patients

Liyi Xie, Li Jin, Jie Feng, Jing Lv, Liyi Xie, Li Jin, Jie Feng, Jing Lv

Abstract

Purpose: To research the distribution and quantitative changes of UT-A1, UT-B1, and AQP5 in uremic skin tissue.

Methods: 34 cases of uremic patients (UP) and 11 controls were recruited. Immunohistochemistry, immunofluorescence, RT-PCR, and Western Blot were used to identify the proteins in sweat glands.

Results: AQP5, UT-A1, and UT-B1 were expressed and localized in human skin basal lines, skin sweat glands, and sweat ducts, both in UP and controls. Compared to controls, AQP5 mRNA abundance was significantly decreased in UP (P < 0.01), and, with the decrease of eGFR, the AQP5 expression was significantly decreased (P < 0.05). By contrast, UT-A1 and UT-B1 mRNA abundance was significantly increased in the skin of UP compared with the control (P < 0.01), and, with the decrease of eGFR, the AQP5 expression was significantly increased (P < 0.05). We found that the gene changes were coincident with the corresponding target proteins. The urea transporter subtypes, UT-A1 and UT-B1, were expressed in the skin basal cell layer and exocrine sweat glands. The abundance of UT-A1 and UT-B1 in uremic sweat glands was significantly increased in UP, while the expression of AQP5 was decreased.

Conclusion: Elimination of urea through the skin by producing sweat is a potential therapeutic strategy for renal failure patients.

Figures

Figure 1
Figure 1
Observation of skin and sweat glands with HE staining. (a) (×40), full-thickness skin showed that sweat gland catheter opened through the epidermis to the skin surface; (b) (×200), subdermal sweat glands are clustered () or distributed separately (#); (c) (×400), the secretion portion (★) and catheter portion (◆) of exocrine sweat glands; (d) (×200), apocrine sweat glands.
Figure 2
Figure 2
Morphologic detection and quantity comparison of sweat gland in human skin. Amounts of sweat glands located in human skin, secretory portion (★), and trochlea portion (◆) are detected. Comparing with the control (a), the shape and size of sweat gland in uremia (b) were of no difference. The number was similar between 3 subgroups (▲ = P > 0.05) (c).
Figure 3
Figure 3
The immunofluorescence examination of the UTs in eccrine sweat glands.
Figure 4
Figure 4
Expression of AQP5, UT-A1, and UT-B1 in skin tissue by immunohistochemistry. (a1), (c1) (×40); (b1), (b2), (b3), (b4) (×200); (a2), (c2), (a3), (c3), (a4), (c4), (a5), (b5), (c5) (×400). FS: full-thickness skin; PC: positive control; UP: uremic patients; NMC: normal controls; NGC: negative control.
Figure 5
Figure 5
Semiquantitative analysis of the expression of AQP5, UT-A1, and UT-B1. Comparison of AQP5, UT-A1, and UT-B1 protein expression in each group. P < 0.01; #P < 0.05.
Figure 6
Figure 6
Expression of AQP5, UT-A1, and UT-B1 mRNA in human skin. P < 0.01; #P < 0.05.
Figure 7
Figure 7
The relative expression of AQP5, UT-A1, and UT-B1 protein in human skin. P < 0.01; #P < 0.05.

References

    1. Huang C. T., Chen M. L., Huang L. L., Mao I. F. Uric acid and urea in human sweat. The Chinese Journal of Physiology. 2002;45(3):109–115.
    1. Watabe A., Sugawara T., Kikuchi K., Yamasaki K., Sakai S., Aiba S. Sweat constitutes several natural moisturizing factors, lactate, urea, sodium, and potassium. Journal of Dermatological Science. 2013;72(2):177–182. doi: 10.1016/j.jdermsci.2013.06.005.
    1. Ilori T. O., Blount M. A., Martin C. F., Sands J. M., Klein J. D. Urine concentration in the diabetic mouse requires both urea and water transporters. American Journal of Physiology-Renal Physiology. 2013;304(1):F103–F111. doi: 10.1152/ajprenal.00385.2012.
    1. Keller R. W., Bailey J. L., Wang Y., Klein J. D., Sands J. M. Urea transporters and sweat response to uremia. Physiological Reports. 2016;4(11) doi: 10.14814/phy2.12825.e12825
    1. Takata K., Matsuzaki T., Tajika Y. Aquaporins: water channel proteins of the cell membrane. Progress in Histochemistry and Cytochemistry. 2004;39(1):1–83. doi: 10.1016/j.proghi.2004.03.001.
    1. Bagnasco S. M., Peng T., Janech M. G., Karakashian A., Sands J. M. Cloning and characterization of the human urea transporter UT-A1 and mapping of the human Slc14a2 gene. American Journal of Physiology-Renal Physiology. 2001;281(3):F400–F406.
    1. Fenton R. A., Cottingham C. A., Stewart G. S., Howorth A., Hewitt J. A., Smith C. P. Structure and characterization of the mouse UT-A gene (Slc14a2) American Journal of Physiology-Renal Physiology. 2002;282(4):F630–F638. doi: 10.1152/ajprenal.00264.2001.
    1. Wei G., Rosen S., Dantzler W. H., Pannabecker T. L. Architecture of the human renal inner medulla and functional implications. American Journal of Physiology-Renal Physiology. 2015;309(7):F627–F637. doi: 10.1152/ajprenal.00236.2015.
    1. Couriaud C., Ripoche P., Rousselet G. Cloning and functional characterization of a rat urea transporter: Expression in the brain. Biochimica et Biophysica Acta—Gene Structure and Expression. 1996;1309(3):197–199. doi: 10.1016/S0167-4781(96)00172-8.
    1. Fenton R. A., Howorth A., Cooper G. J., Meccariello R., Morris I. D., Smith C. P. Molecular characterization of a novel UT-A urea transporter isoform (UT-A5) in testis. American Journal of Physiology-Cell Physiology. 2000;279(5):C1425–C1431.
    1. Inoue H., Jackson S. D., Vikulina T., Klein J. D., Tomita K., Bagnasco S. M. Identification and characterization of a Kidd antigen/UT-B urea transporter expressed in human colon. American Journal of Physiology-Cell Physiology. 2004;287(1):C30–C35. doi: 10.1152/ajpcell.00443.2003.
    1. Stewart G. S., Fenton R. A., Thévenod F., Smith C. P. Urea Movement Across Mouse Colonic Plasma Membranes Is Mediated by UT-A Urea Transporters. Gastroenterology. 2004;126(3):765–773. doi: 10.1053/j.gastro.2003.11.045.
    1. Wang K., Liu H., He Y., et al. Correlation of TLR1-10 expression in peripheral blood mononuclear cells with chronic hepatitis B and chronic hepatitis B-related liver failure. Human Immunology. 2010;71(10):950–956. doi: 10.1016/j.humimm.2010.07.013.
    1. Al-Tamer Y. Y., Hadi E. A., Al-Badrani I. E. I. Sweat urea, uric acid and creatinine concentrations in uraemic patients. Urolithiasis. 1997;25(5):337–340. doi: 10.1007/BF01294662.
    1. Mohan D., Railey M. Uremic frost. Kidney International. 2012;81(11):p. 1153. doi: 10.1038/ki.2012.70.
    1. Karabasil M. R., Murdiastuti K., Purwanti N., et al. Effects of natural point mutation of rat aquaporin 5 expressed in vitro on its capacity of water permeability and membrane trafficking. Journal of Medical Investigation. 2009;56:398–400. doi: 10.2152/jmi.56.398.
    1. Inoue R., Sohara E., Rai T., et al. Immunolocalization and translocation of aquaporin-5 water channel in sweat glands. Journal of Dermatological Science. 2013;70(1):26–33. doi: 10.1016/j.jdermsci.2013.01.013.
    1. Yamamura Y., Motegi K., Kani K., et al. TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation. Journal of Cellular and Molecular Medicine. 2012;16(8):1766–1775. doi: 10.1111/j.1582-4934.2011.01456.x.
    1. Klein J. D., Sands J. M. Urea transport and clinical potential of urearetics. Current Opinion in Nephrology and Hypertension. 2016;25(5):444–451. doi: 10.1097/MNH.0000000000000252.
    1. Sands J. M., Timmer R. T., Gunn R. B. Urea transporters in kidney and erythrocytes. American Journal of Physiology-Renal Physiology. 1997;273(3 part 2):F321–F339.

Source: PubMed

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