SPARC通过磷酸化p38-MAPK信号通路调控角膜缘干细胞生物学特性的机制研究

项目名称： SPARC通过磷酸化p38-MAPK信号通路调控角膜缘干细胞生物学特性的机制研究

项目编号： No.81500696

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 朱婧

作者单位： 山东大学

项目金额： 18万元

中文摘要： 角膜缘干细胞（LSCs）是维持角膜生理功能的关键, LSCs失代偿（LSCD）会导致不可逆视力损害。LSCD治疗主要依赖LSCs移植。植片中LSCs数量显著影响移植成功率：植片内LSCs＜3%时移植成功率<10% 。我们前期研究表明，富含半胱氨酸的酸性分泌蛋白（SPARC）在眼表仅表达于角膜缘基底膜，LSCs仅见于SPARC表达区。故我们推断SPARC与LSCs特性维持密切相关。SPARC可激活p38-MAPK信号通路磷酸化，增强细胞的增殖及迁移能力，维持干细胞池稳定；p38-MAPK信号通路在LSCs中亦有表达。而SPARC与p38-MAPK通路在LSCs特性维持中的机制尚不清楚。据此，本研究提出①SPARC有助于LSCs特性维持②SPARC通过p38-MAPK信号通路磷酸化调控LSCs特性维持。本研究将深化对LSCs特性维持机制的认识，为提高LSCs移植成功率，治疗LSCD开拓新思路。

中文关键词： 富含半胱氨酸的酸性分泌蛋白；p38-MAPK信号通路；角膜缘干细胞；角膜缘干细胞失代偿；移植

英文摘要： Limbal stem cells (LSCs) are the basis of cornea physiological function. Severe ocular surface disease could cause limbal stem cell deficiency (LSCD), and lead to irreversible visual damage. LSCs transplantation is the best way to cure LSCD. The success rate of LSCs transplantation is severely influenced by the number of LSCs in graft—when LSCs number was less than 3% in graft, the transplantation success rate was no more than 10%. Our previous research showed that secreted protein acidic and rich in cysteine (SPARC) only existed in the basement membrane of limbus, and interestingly LSCs were also only found in the region where SPARC expressed. Hereby, we infer that SPARC might promote LSCs physiological function. The phosphorylation of p38-mitogen-activated protein kinase (p38-MAPK) signal pathway could enhance the proliferation of stem cell, mediate asymmetric division of stem cell, and replenish the stem pool; and the expression of phosphorylated p38-MAPK was observed in LSCs. Recent limited research proved that SPARC could enhance the proliferation and migration of tumor stem cell by the activation of p38-MAPK phosphorylation. However, how SPARC and the phosphorylation of p38-MAPK signal pathway mediate LSCs physiological function was still unclear. Accordingly, we hypothesize that 1) SPARC is indispensable to the maintenance of LSCs physiological function; 2) SPARC mediate the physiological function of LSCs mainly through the phosphorylation of p38-MAPK signal pathway. Our research could deepen the comprehension of the molecular mechanism in LSCs maintenance, promote the transplantation success rate, and provide a new method for LSCD therapy.

英文关键词： secreted protein acidic and rich in cysteine;p38-MAPK signal pathway;limbal stem cell;limbal stem cell deficiency;transplantation