ArticleJournal of cellular physiology2012
Src family kinases regulate renal epithelial dedifferentiation through activation of EGFR/PI3K signaling.
Article in Journal of cellular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
- Article
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- KIFC3 Promotes Proliferation, Migration, and Invasion in Colorectal CancerFrontiers in genetics · 2022Article
- BMPER Ameliorates Renal Fibrosis by Inhibiting Tubular Dedifferentiation and Fibroblast Activation.Frontiers in cell and developmental biology · 2021Article
- Proliferative signaling by ERBB proteins and RAF/MEK/ERK effectors in polycystic kidney disease.Cellular signalling · 2020Review
- Metabolic characterization of directly reprogrammed renal tubular epithelial cells (iRECs).Scientific reports · 2018Article
- Exosome production and its regulation of EGFR during wound healing in renal tubular cells.American journal of physiology. Renal physiology · 2017Article
- BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells.Nucleic acids research · 2017Article
- Hyperhomocysteinemia Exacerbates Cisplatin-induced Acute Kidney Injury.International journal of biological sciences · 2017Article
- Epidermal growth factor receptor inhibition with erlotinib partially prevents cisplatin-induced nephrotoxicity in rats.PloS one · 2014Article
- EGFR activity is required for renal tubular cell dedifferentiation and proliferation in a murine model of folic acid-induced acute kidney injury.American journal of physiology. Renal physiology · 2013Article
- Immunohistochemical analysis of vimentin in oral submucous fibrosis.Journal of cancer epidemiology · 2013Article
- A look at transactivation of the EGF receptor by angiotensin II.Journal of the American Society of Nephrology : JASN · 2012Article
- Impaired wound healing in hypoxic renal tubular cells: roles of hypoxia-inducible factor-1 and glycogen synthase kinase 3β/β-catenin signaling.The Journal of pharmacology and experimental therapeutics · 2012Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Dedifferentiation, a process by which differentiated cells become mesenchymal-like proliferating cells, is the first step in renal epithelium repair and occurs in vivo after acute kidney injury and in vitro in primary culture. However, the underlying mechanism remains poorly understood. In this report, we studied the signaling events that mediate dedifferentiation of proximal renal tubular cells (RPTC) in primary culture. RPTC dedifferentiation characterized by increased expression of vimentin concurrent with decreased expression of cytokeratin-18 was observed at 24 h after the initial plating of freshly isolated proximal tubules and persisted for 72 h. At 96 h, RPTC started to redifferentiate as revealed by reciprocal expression of cytokeratin-18 and vimentin and completed at 120 h. Phosphorylation levels of Src, epidermal growth factor receptor (EGFR), AKT (a target of phosphoinositide-3-kinase (PI3K)), and ERK1/2 were increased in the early time course of culture (<72 h). Inhibition of Src family kinases (SFKs) with PP1 blocked EGFR, AKT, and ERK1/2 phosphorylation, as well as RPTC dedifferentiation. Inhibition of EGFR with AG1478 also blocked AKT and ERK1/2 phosphorylation and RPTC dedifferentiation. Although inactivation of the PI3K/AKT pathway with LY294002 inhibited RPTC dedifferentiation, blocking the ERK1/2 pathway with U0126 did not show such an effect. Moreover, inhibition of SFKs, EGFR, PI3K/AKT, but not ERK1/2 pathways abrogated RPTC outgrowth and SFK inhibition decreased RPTC proliferation and migration. These findings demonstrate a critical role of SFKs in mediating RPTC dedifferentiation through activation of the EGFR/PI3K signaling pathway.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.