Yap, the Nuclear Target of Hippo Signaling, Regulates Nasal Epithelium Stem Cells Aberrant Proliferation and Differentiation in Nasal Polyps
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- location of YAP in tissues
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •The Poor Health
- •Be allergic to anesthetics
研究组 & 干预措施
nasal polyps
- 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.
干预措施: functional endonasal sinus surgery (Procedure)
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.
干预措施: nasal septal construction (Procedure)
结局指标
主要结局
location of YAP in tissues
时间窗: through study completion, an average of 2 years
through Immunohistochemistry
protein expression level of YAP in tissues
时间窗: through study completion, an average of 2 years
through western blot
次要结局
- expression level of Th1 cytokines in the tissues(through study completion, an average of 2 years)
- expression level of Th17 cytokines in the tissues(through study completion, an average of 2 years)
- activation of hippo-YAP in NSECs on gene aspect(through study completion, an average of 2 years)
- activation of hippo-YAP in NSECs(through study completion, an average of 2 years)
- activation of hippo-YAP in NSECs on protein aspect(through study completion, an average of 2 years)
研究者
Deng Huiyi
Postgraduate, Head of Otolaryngology, Principal Investigator
Third Affiliated Hospital, Sun Yat-Sen University