Abstract：
Krüppel-like factor 13 (KLF13), a zinc finger transcription factor, is considered as a potential regulator of cardiomyocyte differentiation and proliferation during heart morphogenesis. However, its precise role in the dedifferentiation of vascular smooth muscle cells (VSMCs) during atherosclerosis and neointimal formation after injury remains poorly understood. In this study, we investigated the relationship between KLF13 and SM22α expression in normal and atherosclerotic plaques by bioanalysis, and observed a significant increase in KLF13 levels in the atherosclerotic plaques of both human patients and ApoE-/- mice. Knockdown of KLF13 was found to ameliorate intimal hyperplasia following carotid artery injury. Furthermore, we discovered that KLF13 directly binds to the SM22α promoter, leading to the phenotypic dedifferentiation of VSMCs. Remarkably, we observed a significant inhibition of platelet-derived growth factor BB-induced VSMCs dedifferentiation, proliferation, and migration when knocked down KLF13 in VSMCs. This inhibitory effect of KLF13 knockdown on VCMC function was, at least in part, mediated by the inactivation of p-AKT signaling in VSMCs. Overall, our findings shed light on a potential therapeutic target for treating atherosclerotic lesions and restenosis after vascular injury.
摘要：
Krüppel样因子13（KLF13），锌指转录因子,被认为是心脏形态发生过程中心肌细胞分化和增殖的潜在调节剂。然而,其在动脉粥样硬化和损伤后新内膜形成过程中血管平滑肌细胞（VSMC）去分化中的确切作用尚不清楚。在这项研究中,我们通过生物分析研究了正常和动脉粥样硬化斑块中KLF13和SM22α表达之间的关系，并观察到人类患者和ApoE-/-小鼠的动脉粥样硬化斑块中KLF13水平的显着增加。发现KLF13敲除可改善颈动脉损伤后的内膜增生。此外，我们发现KLF13直接与SM22α启动子结合，导致VSMC的表型去分化。值得注意的是,我们观察到血小板源性生长因子BB诱导的VSMCs去分化的显著抑制，扩散,以及在VSMC中击倒KLF13时的迁移。KLF13敲低对VCMC功能的抑制作用是，至少在某种程度上,由VSMC中p-AKT信号失活介导。总的来说,我们的研究结果揭示了治疗动脉粥样硬化病变和血管损伤后再狭窄的潜在治疗靶点.
