YAP1调控间质成纤维细胞活化的研究进展
作者: |
1肖颖,
1张卉,
1刘彤华
1 北京协和医院病理科,北京 100730 |
通讯: |
刘彤华
Email: Tonghua_liu@163.com |
DOI: | 10.3978/j.issn.2095-6959.2017.08.027 |
基金: | 国家自然科学基金, 81502625 |
摘要
间质成纤维细胞位于实质细胞周围,参与细胞外基质(extracellular matrix,ECM)分泌。该细胞通常处于静止状态,但在炎症和肿瘤等疾病发生时异常活化。成纤维细胞活化受多种基因调控,这些基因通过促进细胞增殖、促进胶原蛋白和纤维蛋白等ECM分泌,导致局部组织过度纤维化,促进疾病进展。Yes相关蛋白1(Yes-associated protein 1,YAP1)是一种转录因子共刺激分子,同时也是多种信号通路的效应分子。YAP1在活化状态成纤维细胞内表达水平较高。且该蛋白通过调控包含生长因子在内的活化相关的基因表达,可促进成纤维细胞活化。因此,YAP1可能是成纤维细胞活化的关键调控因子,下调YAP1表达有望成为纤维化疾病的潜在治疗方式。
关键词:
Yes相关蛋白1
成纤维细胞
活化
纤维化
细胞微环境
Research progress in regulation of activating stromal fibroblasts by YAP1
CorrespondingAuthor: LIU Tonghua Email: Tonghua_liu@163.com
DOI: 10.3978/j.issn.2095-6959.2017.08.027
Abstract
Stromal fibroblasts are located in the surrounding of parenchyma cells and involved in secretion of extracellular matrix (ECM). The cells are quiescent in general state, but abnormally activated when diseases such as inflammation and tumors occur. The activation of fibroblasts is regulated by various genes, which can promote cell proliferation and secretion of ECM like collagen and fibrin, thus leading to disease progression induced by excessive local fibrosis. Yes-associated protein 1 (YAP1) is not only a coactivator of transcription factor, but also an effector in multiple signaling pathways. The expression level of YAP1 is up-regulated in activated fibroblast. Moreover, the protein could contribute to activation of fibroblasts through regulating the expression of activation-related genes like growth factors. As a result, YAP1 may be a key regulator in fibroblast activation, and inhibition of YAP is expected to be a potential treatment of fibrosis.
Keywords:
Yes-associated protein 1
fibroblast
activation
fibrosis
cellular microenvironment