The Activation of Hippo Pathway in Nasal Polyps

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Nasal Polyps

Intervention / Treatment
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* Procedure: functional endonasal sinus surgery
* Procedure: nasal septal construction


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: nasal polyps<br>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. 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. Explore that how the hippo-YAP effect the proliferation and differentiation of NESCs through cell transfection; Explore the regulation of hippo-YAP pathway in NESCs. | Procedure: functional endonasal sinus surgery<br>* collect nasal polyps from patients<br>* Other names: FESS;|
| Placebo Comparator: inferior turbinate<br>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<br>* collect inferior turbinates from patients as control arm<br>|

What is the study measuring?
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Primary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nasal epithelium stem cells, Hippo-YAP pathway, proliferation, differentiation