早期生长反应因子 1 通过转录调控高糖处理的 HK-2 细胞中 PAR1 来激活 TGF-β1/Smad 通路，从而上调致纤维化基因。
Early growth response factor 1 upregulates pro-fibrotic genes through activation of TGF-β1/Smad pathway via transcriptional regulation of PAR1 in high-glucose treated HK-2 cells.
机构信息
Department of Endocrinology and Metabolism, Shenzhen People's Hospital, The second Clinical Medical College of Jinan University, The First Affiated Hospital, Southern University of Science and Technology, Shenzhen, 518020, Guangdong, China.
Department of Pharmacy, Shenzhen People's Hospital, The second Clinical Medical College of Jinan University, The First Affiated Hospital, Southern University of Science and Technology, Shenzhen, 518020, Guangdong, China.
出版信息
Mol Cell Endocrinol. 2023 Jul 15;572:111953. doi: 10.1016/j.mce.2023.111953. Epub 2023 May 10.
Tubulointerstitial fibrosis (TIF) makes a key role in diabetic kidney disease (DKD). In this study, we revealed that the expressions of Egr1 and protease-activated receptor 1 (PAR1) were increased in renal tissues of DKD rats. In vitro experiments demonstrated that both Egr1 overexpression and high glucose (HG) condition could promote the expressions of PAR1, fibronectin (FN) and collagen I (COL I). Furthermore, HG stimulation enhanced the binding capacity of Egr1 to PAR1 promoter. Both HG condition and Egr1 upregulation could increase, and thrombin inhibitor did not affect activity of TGF-β1/Smad pathway via PAR1. Collectively, Egr1 is involved in TIF of DKD partly through activating TGF-β1/Smad pathway via transcriptional regulation of PAR1 in HG treated HK-2 cells.
肾小管间质纤维化（TIF）在糖尿病肾病（DKD）中起着关键作用。在这项研究中，我们揭示了 Egr1 和蛋白酶激活受体 1（PAR1）的表达在 DKD 大鼠的肾脏组织中增加。体外实验表明，Egr1 过表达和高葡萄糖（HG）条件均可促进 PAR1、纤维连接蛋白（FN）和胶原 I（COL I）的表达。此外，HG 刺激增强了 Egr1 与 PAR1 启动子的结合能力。HG 条件和 Egr1 上调均可增加，而凝血酶抑制剂不通过 PAR1 影响 TGF-β1/Smad 通路的活性。总之，Egr1 部分通过在 HG 处理的 HK-2 细胞中通过 PAR1 的转录调控激活 TGF-β1/Smad 通路参与 DKD 的 TIF。
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