下调和上调
生物
血管生成
血管生成
内皮功能障碍
内皮干细胞
背景(考古学)
细胞生物学
脐静脉
TXNIP公司
内分泌学
癌症研究
基因
氧化应激
生物化学
体外
古生物学
硫氧还蛋白
作者
Renan Chen,Xiaoli Sun,Chuan Yan,Li Liu,Ming Hao,Qiang Liu,Xi-Ying Jiao,Ying‐Min Liang
标识
DOI:10.1016/j.bbrc.2016.06.052
摘要
Vascular endothelial dysfunction, a central hallmark of diabetes, predisposes diabetic patients to numerous cardiovascular complications. The POZ/BTB and AT-hook-containing zinc finger protein 1 (PATZ1), is an important transcriptional regulatory factor and regulates divergent pathways depending on the cellular context, but its role in endothelial cells remains poorly understood. Herein, we report for the first time that endothelial PATZ1 expression was abnormally upregulated in diabetic endothelial cells (ECs) regardless of diabetes classification. This stimulatory effect was further confirmed in the high glucose-treated human umbilical vein endothelial cells (HUVECs). From a functional standpoint, transgenic overexpression of PATZ1 in endothelial colony forming cells (ECFCs) blunted angiogenesis in vivo and rendered endothelial cells unresponsive to established angiogenic factors. Mechanistically, PATZ1 acted as a potent transcriptional corepressor of fatty acid-binding protein 4 (FABP4), an essential convergence point for angiogenic and metabolic signaling pathways in ECs. Taken together, endothelial PATZ1 thus potently inhibits endothelial function and angiogenesis via inhibition of FABP4 expression, and abnormal induction of endothelial PATZ1 may contribute to multiple aspects of vascular dysfunction in diabetes.
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