دورية أكاديمية

Epidermal growth factor receptor activation is essential for kidney fibrosis development.

التفاصيل البيبلوغرافية
العنوان: Epidermal growth factor receptor activation is essential for kidney fibrosis development.
المؤلفون: Cao, Shirong, Pan, Yu, Terker, Andrew S., Arroyo Ornelas, Juan Pablo, Wang, Yinqiu, Tang, Jiaqi, Niu, Aolei, Kar, Sarah Abu, Jiang, Mengdi, Luo, Wentian, Dong, Xinyu, Fan, Xiaofeng, Wang, Suwan, Wilson, Matthew H., Fogo, Agnes, Zhang, Ming-Zhi, Harris, Raymond C.
المصدر: Nature Communications; 11/14/2023, Vol. 14 Issue 1, p1-17, 17p
مصطلحات موضوعية: RENAL fibrosis, KIDNEY development, URETERIC obstruction, EPIDERMAL growth factor receptors
مستخلص: Fibrosis is the progressive accumulation of excess extracellular matrix and can cause organ failure. Fibrosis can affect nearly every organ including kidney and there is no specific treatment currently. Although Epidermal Growth Factor Receptor (EGFR) signaling pathway has been implicated in development of kidney fibrosis, underlying mechanisms by which EGFR itself mediates kidney fibrosis have not been elucidated. We find that EGFR expression increases in interstitial myofibroblasts in human and mouse fibrotic kidneys. Selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins. In vivo and in vitro studies and single-nucleus RNA sequencing analysis demonstrate that EGFR activation does not induce myofibroblast transformation but is necessary for the initial pericyte/fibroblast migration and proliferation prior to subsequent myofibroblast transformation by TGF-ß or other profibrotic factors. These findings may also provide insight into development of fibrosis in other organs and in other conditions. Fibrosis is the progressive accumulation of excess extracellular matrix produced by myofibroblasts leading to organ failure. Here the authors show that expression of the Epidermal Growth Factor Receptor (EGFR) increases in interstitial myofibroblasts in human and mouse fibrotic kidneys, and selective EGFR deletion in the fibroblast/pericyte population inhibits interstitial fibrosis in response to unilateral ureteral obstruction, ischemia or nephrotoxins. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:20411723
DOI:10.1038/s41467-023-43226-x