表皮生长因子受体激活刺激损伤肾近端小管上皮细胞中SOX9的表达。

IF 9.4 1区 医学 Q1 UROLOGY & NEPHROLOGY
Jianchun Chen, Fenfen Peng, Mengdi Jiang, Shirong Cao, Chen Zhao, Ming-Tsun Tsai, Yinqiu Wang, Agnes B Fogo, Ming-Zhi Zhang, Raymond C Harris
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引用次数: 0

摘要

背景:在急性肾损伤(AKI)后存活的肾近端小管细胞(RPTCs)中,诱导SOX9表达在促进肾脏修复中起着至关重要的作用。然而,RPTCs中SOX9的持续上调有助于慢性肾脏疾病(CKD)的发展。SOX9诱导肾损伤的分子机制尚不完全清楚。我们和其他人之前报道过,RPTCs中表皮生长因子受体(EGFR)的激活可以加速肾从缺血性损伤中恢复,但持续的EGFR激活会导致小管间质纤维化。方法:检测急性肾小管损伤或早期慢性肾移植肾病患者肾小管上皮细胞中SOX9和EGFR的表达。我们使用不同的小鼠模型研究了EGFR激活在损伤rptc中调节SOX9上调的作用。我们进一步证实了EGFR激活在培养的人RPTCs中上调SOX9表达的潜在机制。结果:急性肾小管损伤或慢性肾移植肾病早期患者肾小管上皮细胞中均检测到SOX9和EGFR表达的升高和共定位。hHB-EGF在小鼠RPTC中的过表达导致SOX9表达增加,当这些小鼠与EGFR酪氨酸激酶缺陷的Wa2小鼠杂交时,SOX9表达被消除。基因或药物抑制EGFR导致肾小管细胞中SOX9表达降低,以应对缺血性AKI。机制上,缺血性AKI激活近端小管EGFR,导致Akt-YAP/TAZ-TEAD通路激活,随后诱导SOX9。结论:EGFR激活对于AKI后RPTCs中SOX9的表达至关重要。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
EGF Receptor Activation Stimulates SOX9 Expression in Injured Renal Proximal Tubule Epithelial Cells.
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来源期刊
Journal of The American Society of Nephrology
Journal of The American Society of Nephrology 医学-泌尿学与肾脏学
CiteScore
22.40
自引率
2.90%
发文量
492
审稿时长
3-8 weeks
期刊介绍: The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews. Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication. JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.
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