富含Fibrillin 1的组织微环境对成纤维细胞增殖与活化的作用及机制

成纤维细胞增殖与活化是导致慢性肾脏病（Chronic Kidney Disease, CKD）中肾脏纤维化的关键因素。我们近期研究表明富含Fibrillin 1的组织微环境在驱动CKD中内皮细胞损伤和血管稀疏化方面发挥着重要作用，但其能否调控成纤维细胞的增殖与活化尚不清楚。本项目旨在探讨富含Fibrillin 1的组织微环境对成纤维细胞增殖与活化的作用及机制。我们提出：富含Fibrillin 1的组织微环境通过激活MAPK信号通路诱导成纤维细胞的增殖与活化。为验证这一假说，我们将通过构建多种CKD小鼠模型和Fibrillin 1基因条件性敲除小鼠，分别在体外和体内研究Fibrillin 1对成纤维细胞增殖与活化的作用和机制，并深入探讨敲除Fibrillin 1对成纤维细胞增殖与活化和肾脏纤维化的影响。这些研究对阐明慢性肾脏病纤维化的发生机制、制定有效的干预策略具有重要意义。

Fibroblast proliferation and activation are the key factors leading to renal fibrosis in chronic kidney disease (CKD). Our recent studies have shown that Fibrillin 1–enriched microenvironment drives endothelial injury and vascular rarefaction in chronic kidney disease, but it is unclear whether it can regulate the proliferation and activation of fibroblasts. This project aims to explore the effect and molecular mechanism of the Fibrillin 1–enriched microenvironment on the proliferation and activation of fibroblasts. We propose that the Fibrillin 1–enriched microenvironment induces the proliferation and activation of fibroblasts through the MAPK signaling pathway. In order to verify this hypothesis, we will construct a variety of CKD mouse models and Fibrillin 1 gene conditional knockout mouse model. We will study the effects and mechanisms of Fibrillin 1 on the proliferation and activation of fibroblasts in vitro and in vivo, and further explore the effects of knocking out Fibrillin 1 on the proliferation and activation of fibroblasts and renal fibrosis. These studies are of great significance for elucidating the mechanism of chronic kidney disease fibrosis and formulating effective intervention strategies.