血管重构是高血压发生、发展的重要病理基础，但调控血管重构的信号通路尚未阐明清楚。本课题组最近发现二氧化硫通过抑制TGF-beta/Smad信号通路缓解血管平滑肌细胞胶原重构。在上述研究基础上本项目拟采用探针标记和质谱分析，从整体、细胞和分子水平揭示二氧化硫对Smad3锌指结构半胱氨酸存在次磺化修饰作用；在Samd3半胱氨酸点突变基因敲入小鼠中，给予血管紧张素II诱导高血压模型，研究二氧化硫对Smad3信号通路活化的调节作用以及二氧化硫诱导的Smad3次磺化修饰对高血压血管重构的调节效应；从Smad3锌指结构和DNA结合能力切入，揭示二氧化硫介导的Smad3次磺化修饰抑制Smad3信号活化的分子机制。通过上述研究，以期揭示二氧化硫对Smad3蛋白新的调控方式—次磺化修饰，进一步深化二氧化硫对高血压血管重构的调节机制理论，为探寻高血压的有效治疗新靶点提供新的研究思路。

Vascular remodeling is one of important pathology in the formation and development of hypertension. However, the signaling pathways regulating vascular remodeling have not been clarified. Our research group recently found that sulfur dioxide alleviated collagen remodeling in vascular smooth muscle cells through inhibiting TGF-beta/Smad signaling pathway. Based on the above studies, the present study is designed to investigate the sulfenylation of Smad3 on cysteine of its zinc finger domain induced by sulfur dioxide in vivo and in vitro using probe labeling and mass spectrometry analysis and investigate the effect of sulfenylation of Smad3 induced by sulfur dioxide on the activation of Smad3 signaling pathway and hypertensive vascular remodeling in the cysteine-mutated Smad3 knock-in mice infused with angiotensin II and in the cells. Targeting on the zinc finger domain of Smad3 and its DNA binding ability, the study aims to explore the molecular mechanisms by which the sulfur dioxide-induced sulfenylation of Smad3 inhibited the activation of Smad3 signaling. The study would reveal the new regulatory way of Smad3 protein by sulfur dioxide and further deepen the regulatory theory of Smad3 signaling pathway mediated by sulfur dioxide in hypertensive vascular remodeling, providing the new research direction for novel targets of effective treatment of hypertension.