心肌纤维化是心脏疾病常见的病理生理改变，有多种因子和信号通路参与纤维化生成。FGF23（fibroblast growth factor 23）是骨/心源性内分泌因子，与心肌纤维化密切相关；Klotho是FGF23潜在的调控因子，但Klotho/FGF23信号通路在心脏中的调控尚无报道。我们前期研究发现：外源性给予Klotho能够上调促纤维化因子Col-I的表达，敲减心脏肌成纤维细胞中表达的Klotho蛋白能够显著抑制FGF23 mRNA的表达。因此，我们假设：Klotho通过调节FGF23参与调控心肌纤维化。本项目运用多种分子生物学手段探讨：1）Klotho是否参与心肌纤维化过程；2）Klotho是否通过FGF23诱导心肌纤维化及其下游机制。本项目有助于阐明心肌纤维化发生的新机制，发现新的防治靶点，促进新型药物研发。

Cardiac fibrosis is a common pathophysiological changes of cardiovascular disease and various factors and signal pathways are involved in fibrogenesis. FGF23（fibroblast growth factor 23）a bone/heart endocrine factor is associated with cardiac fibrogenesis. Klotho is a potential regulator for FGF23，and the role of Klotho/FGF23 signal pathway has not been identified in cardiac fibrosis. Our previous study found that exogenous administration of Klotho up-regulated Col-I synthesis and knockdown of Klotho in myofibroblasts reduced FGF23 expression. Therefore, we hypothesized that Klotho is involved in the development of cardiac fibrosis by regulating FGF23. We will use various molecular biology techniques to varify the following hypothesis: 1) To detect whether Klotho is involved in cardiac fibrosis. 2) To investigate whether Klotho regulates cardiac fibrosis via FGF23 and its downstream mechanism. The findings of our study will reveal a new mechanism of cardiac fibrosis, discover a novel therapeutic target and promote new drug development.