The Activation of Hippo Pathway in Nasal Polyps

September 10, 2018 updated by: Deng Huiyi, Third Affiliated Hospital, Sun Yat-Sen University

Yap, the Nuclear Target of Hippo Signaling, Regulates Nasal Epithelium Stem Cells Aberrant Proliferation and Differentiation in Nasal Polyps

Hippo-YAP pathway is a newly discovered pathway controlling the growth, and plays important roles in the regulation of stem cell function and tissue regeneration. Previously we found that a higher expression of YAP in NP, and LPS was able to activate the hippo-YAP pathway in NESCs. Thus, we hypothesize that the aberrant proliferation and differentiation of NESCs could be regulated via the hippo-YAP pathway.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Studies have shown that the development of nasal polyps (NP) are closely related to the epithelial remodeling.The investigators have shown that nasal epithelial stem cells(NESCs) derived from NP had reduced growth and proliferation dynamics in vitro culture,and differentiated into ciliated cells with impaired cilia architecture and ciliogenesis.Further studies demonstrated that NESCs were involved in the aberrant damage repair process of the epithelial remodeling in NP.Hippo-YAP pathway is a newly discovered pathway controlling the growth,and plays important roles in the regulation of stem cell function and tissue regeneration.Previously the investigators found that a higher expression of YAP in NP,and LPS was able to activate the hippo-YAP pathway in NESCs.Thus,the investigators hypothesize that the aberrant proliferation and differentiation of NESCs could be regulated via the hippo-YAP pathway,which may result in the epithelial remodeling.In this study,the investigators intend to investigate the mechanism of the hippo-YAP pathway in regulating aberrant proliferation and differentiation of NESCs and explore its upstream signaling and downstream target genes,using the NESCs gas-liquid interface culture system,and a silencing and overexpression of the hippo-YAP pathway component strategy.The investigators aim to unravel the effect and mechanism of the hippo-YAP pathway in the epithelial remodeling of NP,providing new targets and strategy for the improvement or reversal of NP epithelial remodeling.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510630

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Clinical diagnosis of nasal polyps or deviation of nasal septum based on CT
  • Must be able to withstand surgery
  • At least 18 years old
  • A sufficient level of education to understand study procedures and be able to communicate with site personnel and adhere to the follow-up;
  • Accepted informed consent verbally and in writing

Exclusion Criteria:

  • The Poor Health
  • Be allergic to anesthetics

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: nasal polyps
  1. Explore the degree of abnormal proliferation in NESCs,and analyze the relationship between the proliferation and the activation of hippo-YAP pathway,then explore the levels of LPS and Th2/17 cytokines in nasal polyps,and the relation between cytokines and the activation of hippo-YAP pathway through Immunohistochemistry and Immunofluorescence （P63、Ki67、YAP、LATS1/2 and MST1/2），as well as Western Blot and the Flow cytometry.
  2. Explore if the LPS and LPS and Th2/17 cytokines, as well as the epidermal growth factors can effect the hippo-YAP pathway of NESCs through cell culture, Western Blot and Real time PCR,and test the YAP expression and location through Immunohistochemistry.
  3. Explore that how the hippo-YAP effect the proliferation and differentiation of NESCs through cell transfection;
  4. Explore the regulation of hippo-YAP pathway in NESCs.
Procedure: functional endonasal sinus surgery
collect nasal polyps from patients
Other Names:
  • FESS
Placebo Comparator: inferior turbinate
Compared with nasal polyps,explore the levels of LPS and Th2/17 cytokines in nasal polyps,and the relation between cytokines and the activation of hippo-YAP pathway through Immunohistochemistry and Immunofluorescence（P63、Ki67、YAP、LATS1/2 and MST1/2），as well as Western Blot and the Flow cytometry.
Procedure: nasal septal construction
collect inferior turbinates from patients as control arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
location of YAP in tissues
Time Frame: through study completion, an average of 2 years
through Immunohistochemistry
through study completion, an average of 2 years
protein expression level of YAP in tissues
Time Frame: through study completion, an average of 2 years
through western blot
through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
expression level of Th1 cytokines in the tissues
Time Frame: through study completion, an average of 2 years
through Flow cytometry
through study completion, an average of 2 years
expression level of Th17 cytokines in the tissues
Time Frame: through study completion, an average of 2 years
through Flow cytometry
through study completion, an average of 2 years
activation of hippo-YAP in NSECs on protein aspect
Time Frame: through study completion, an average of 2 years
Western Blot
through study completion, an average of 2 years
activation of hippo-YAP in NSECs
Time Frame: through study completion, an average of 2 years
Flow cytometry
through study completion, an average of 2 years
activation of hippo-YAP in NSECs on gene aspect
Time Frame: through study completion, an average of 2 years
quantitive real time PCR
through study completion, an average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Third Affiliated Hospital, Sun Yat-Sen University

Collaborators

National University of Singapore

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 20, 2017

Primary Completion (Anticipated)

July 31, 2020

Study Completion (Anticipated)

July 31, 2020

Study Registration Dates

First Submitted

April 21, 2017

First Submitted That Met QC Criteria

May 10, 2017

First Posted (Actual)

May 12, 2017

Study Record Updates

Last Update Posted (Actual)

September 11, 2018

Last Update Submitted That Met QC Criteria

September 10, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NSFC-H1301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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