Abstract：
The RNA-binding zinc finger protein 36 (ZFP36) family participates in numerous physiological processes including transition and differentiation through post-transcriptional regulation. ZFP36L1 is a member of the ZFP36 family. This study aimed to evaluate the role of ZFP36L1 in restenosis. We found that the expression of ZFP36L1 was inhibited in VSMC-phenotypic transformation induced by TGF-β, PDGF-BB, and FBS and also in the rat carotid injury model. In addition, we found that the overexpression of ZFP36L1 inhibited the proliferation and migration of VSMCs and promoted the expression of VSMC contractile genes; whereas ZFP36L1 interference promoted the proliferation and migration of VSMCs and suppressed the expression of contractile genes. Furthermore, the RNA binding protein immunoprecipitation and double luciferase reporter gene experiments shows that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16. Finally, our research results in the rat carotid balloon injury animal model further confirmed that ZFP36L1 regulates the phenotypic transformation of VSMCs through the posttranscriptional regulation of KLF16 and further plays a role in vascular injury and restenosis in vivo.
摘要：
RNA结合锌指蛋白36（ZFP36）家族通过转录后调节参与许多生理过程，包括过渡和分化。ZFP36L1是ZFP36家族的成员。本研究旨在评估ZFP36L1在再狭窄中的作用。我们发现ZFP36L1的表达在TGF-β诱导的VSMC表型转化中受到抑制,PDGF-BB,和FBS以及大鼠颈动脉损伤模型。此外,我们发现ZFP36L1的过表达抑制了VSMC的增殖和迁移，促进了VSMC收缩基因的表达；而ZFP36L1的干扰促进了VSMC的增殖和迁移，抑制了收缩基因的表达。此外，RNA结合蛋白免疫沉淀和双荧光素酶报告基因实验表明，ZFP36L1通过KLF16的转录后调控来调控VSMCs的表型转化。最后,我们在大鼠颈动脉球囊损伤动物模型中的研究结果进一步证实，ZFP36L1通过KLF16的转录后调控调节VSMCs的表型转化，进一步在体内血管损伤和再狭窄中发挥作用。
