ZHX2通过GADD45G的转录调控缓解血管重塑和平滑肌细胞增殖
ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.
摘要(中文译文)
基于对人类动脉粥样硬化动脉和小鼠动脉损伤模型的研究发现——在这些模型中ZHX2表达显著下调——本研究确定ZHX2是病理性血管重塑的关键抑制因子。在功能上，体内局部腺病毒过表达ZHX2可减轻小鼠颈动脉结扎模型中的新生内膜形成，而体外实验表明ZHX2阻碍原代血管平滑肌细胞（VSMCs）的增殖和迁移。在机制上，整合RNA-seq和ChIP-seq分析揭示ZHX2在转录水平调控GADD45G，直接结合其启动子并激活其转录。该通路的重要作用通过以下发现得到证实：敲低GADD45G可抵消ZHX2过表达对VSMC增殖、迁移和新生内膜形成的抑制作用。因此，ZHX2/GADD45G信号轴被强调为损伤相关新生内膜重塑中的潜在调控通路。
Abstract
Based on findings from human atherosclerotic arteries and mouse arterial injury models, where ZHX2 expression is significantly downregulated, this study identifies ZHX2 as a critical inhibitor of pathological vascular remodeling. Functionally, local adenoviral overexpression of ZHX2 in vivo attenuates neointima formation in a mouse carotid artery ligation model, while in vitro experiments demonstrate that ZHX2 impedes the proliferation and migration of primary Vascular Smooth Muscle Cells (VSMCs). Mechanistically, integrated RNA-seq and ChIP-seq analyses reveal that ZHX2 transcriptionally regulates GADD45G, directly binding to its promoter and activating its transcription. The essential role of this pathway is confirmed by the finding that knockdown of GADD45G counteracts the inhibitory effects of ZHX2 overexpression on VSMC proliferation, migration, and neointima formation. Consequently, the ZHX2/GADD45G signaling axis is highlighted as a potential regulatory pathway in injury-associated neointimal remodeling.
如何引用
AMA
Siyuan Fan, Xuelian Wu, Lin Gui, Yichen Wu, Baoru Qiao, Yue Li, et al. ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2026; doi:10.1096/fj.202505033R.
APA
Siyuan Fan, Xuelian Wu, Lin Gui, Yichen Wu, Baoru Qiao, Yue Li, et al (2026). ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.202505033R
GB/T 7714
Siyuan Fan, Xuelian Wu, Lin Gui, Yichen Wu, Baoru Qiao, Yue Li, et al. ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.[J]. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026 doi:10.1096/fj.202505033R.
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