肾小管上皮细胞转分化（EMT）是缺血性急性肾损伤（I/R-AKI）后纤维化的早期特征及其慢性化转归的主要原因。血清反应因子（SRF）通过激活Snail诱导EMT，促进肾纤维化。CCN1（Cyr61，富含半胱氨酸蛋白61）在I/R-AKI早期对肾小管上皮细胞具有保护作用，但其对纤维化作用不明确。整合素αvβ3/αvβ5作为CCN1的主要配体，是胞外信号与胞内生长因子之间重要的信号桥梁，CCN1（D125A）突变体可特异性阻断αvβ3/αvβ5。因此我们提出假说：CCN1（D125A）突变体通过阻断αvβ3/αvβ5，减少SRF和Snail的表达，抑制EMT，减缓肾纤维化进程。我们将通过构建转基因动物模型、细胞模型，采用慢病毒载体转染、RNA干扰、Western blot等手段，探讨CCN1（D125A）在I/R-AKI后肾纤维化中的作用，并为I/R-AKI后肾纤维化的防治提供新的干预靶点。

Epithelial-mesenchymal transdifferentiation (EMT) is an early feature of tubulointerstitial fibrosis after acute kidney injury (I/R-AKI), which also is the leading cause of transformation from I/R-AKI to chroinc kidney disease. Activation of serum response factors (SRF) and Snail can significantly induce EMT and promote renal fibrosis. CCN1 (Cyr61) as an immediate secreted protein after injury, has shown protective effects on renal tubular in I/R-AKI, but its effect on renal fibrosis is unclear. Integrin αvβ3/αvβ5, as the main ligand of CCN1, is an important signal bridge between extracellular signals and intracellular growth factors. CCN1 (D125A) specifically blocks the exchange of information between CCN1 and αvβ3/αvβ5. Therefore, we hypothesized that CCN1 (D125A) inhibits EMT by inhibiting αvβ3/αvβ5, reducing the expression of SRF and Snail. We will explore the role of CCN1 in renal fibrosis after I/R-AKI by constructing a transgenic I/R-AKI animal and cell model and using techniques such as lentiviral vector transfection, RNA interference, Western blot, etc. This project will deepen the understanding of the mechanism of renal fibrosis after I/R-AKI, thus providing a newintervention target for clinical prevention and treatment of renal fibrosis after I/R-AKI.