The Activation of Hippo Pathway in Nasal Polyps

Not Applicable

• Conditions: Nasal Polyps
• Interventions: Procedure: nasal septal construction; Procedure: functional endonasal sinus surgery

• Registration Number: NCT03151954
• Lead Sponsor: Third Affiliated Hospital, Sun Yat-Sen University

Brief Summary

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.

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 Timeline

• Study Start: 2017-04-20
• Study First Submitted: 2017-04-21
• Study First Submitted QC: 2017-05-10
• Study First Posted: 2017-05-12
• Status Verified: 2018-09
• Last Update Submitted: 2018-09-10
• Last Update Posted: 2018-09-11
• Primary Completion: 2020-07-31
• Study Completion: 2020-07-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
inferior turbinate	nasal septal construction	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.
nasal polyps	functional endonasal sinus surgery	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.

Primary Outcome Measures

Name	Time	Method
location of YAP in tissues	through study completion, an average of 2 years	through Immunohistochemistry
protein expression level of YAP in tissues	through study completion, an average of 2 years	through western blot

Secondary Outcome Measures

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

Trial Locations

Locations (1)

ThirdSunYatSen; 🇨🇳 Guangzhou, Guangdong, China