川崎病（KD）以全身免疫性中小血管炎为主要特征，常累及冠状动脉，但具体机制尚不清楚。血管内皮损伤修复能力减弱与KD冠状动脉病变形成关系密切。目前公认内皮细胞增殖和迁移参与血管内皮损伤修复环节。我们前期研究证实细胞外基质糖蛋白Tenascin C (TNC)是造成KD冠脉损伤的重要因素，初步分析认为TNC通过结合整合素受体α9β1，抑制RhoA活性，从而影响YAP的转录辅激活活性，进而抑制内皮细胞的增殖和迁移功能，但该机制有待更为详实的确证。我们将首先明确TNC在内皮细胞中发挥作用所需要的受体类型；随后在动物水平进一步验证RhoA是TNC调控内皮细胞功能的关键蛋白；最后在细胞及动物水平确认YAP是TNC发挥效应所需的主要转录辅激活因子。本项目旨在分子水平深入解析TNC抑制血管内皮细胞增殖和迁移功能，进而造成KD冠脉损伤的具体机制，从而为临床上防治KD冠脉损伤提供理论依据。

Kawasaki disease (KD) is mainly characterized by systemic immune vasculitis and often involves coronary arteries, but the specific mechanism is still unknown. The weakened repair ability of vascular endothelial injury is closely related to the formation of KD coronary artery disease. Endothelial cell proliferation and migration are currently recognized as involved in the repair of vascular endothelial injury. Our previous research confirmed that the extracellular matrix glycoprotein Tenascin C (TNC) is an important factor causing KD coronary artery injury. Preliminary analysis suggests that TNC inhibits RhoA activity by binding the integrin receptor α9β1, thereby affecting the transcriptional co-activation activity of YAP, and further inhibits the proliferation and migration of endothelial cells, but the mechanism needs to be confirmed in more detail. We will first identify the types of receptors required for TNC to function in endothelial cells; then further verify that RhoA is a key protein for TNC to regulate endothelial cell function at the animal level; and finally confirm that YAP is the major transcriptional co-activator required for TNC to exert its effects at the cell and animal levels. This project aims to deeply analyze the specific mechanism of TNC inhibiting the proliferation and migration of vascular endothelial cells and then causing the KD coronary injury, so as to provide a theoretical basis for the clinical prevention and treatment of KD coronary artery injury.