ArticleCellular signalling2014
Epidermal growth factor inhibits transforming growth factor-β-induced fibrogenic differentiation marker expression through ERK activation.
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Renal Protection of HWL-088and ZLY-032, Two Dual GPR40/PPARδ Agonists, in Adenine-Induced Renal Fibrosis Model.Chemistry & biodiversity · 2025Article
- The TFEB-TGIF1 axis regulates EMT in mouse epicardial cells.Nature communications · 2022Article
- Rivaroxaban attenuates cardiac hypertrophy by inhibiting protease-activated receptor-2 signaling in renin-overexpressing hypertensive mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Blockade of PAR-1 Signaling Attenuates Cardiac Hypertrophy and Fibrosis in Renin-Overexpressing Hypertensive Mice.Journal of the American Heart Association · 2020Article
- Effects of epidermal growth factor on transforming growth factor-beta1-induced epithelial-mesenchymal transition and potential mechanism in human corneal epithelial cells.International journal of ophthalmology · 2020Article
- ERK1/2 drives IL-1β-induced expression of TGF-β1 and BMP-2 in torn tendons.Scientific reports · 2019Article
- Blocking the histone lysine 79 methyltransferase DOT1L alleviates renal fibrosis through inhibition of renal fibroblast activation and epithelial-mesenchymal transition.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Endoscopic resection of the pancreatic tail and subsequent wound healing mechanisms in a porcine model.World journal of gastroenterology · 2019Article
- The plant alkaloid conophylline inhibits matrix formation of fibroblasts.The Journal of biological chemistry · 2018Article
- TGF-b1 or hypoxia enhance glucose metabolism and lactate production via HIF1A signaling in tendon cells.Connective tissue research · 2018Article
- TGF-β1/Smad2/3/Foxp3 signaling is required for chronic stress-induced immune suppression.Journal of neuroimmunology · 2018Article
- Calpain 1 regulates TGF-β1-induced epithelial-mesenchymal transition in human lung epithelial cells via PI3K/Akt signaling pathway.American journal of translational research · 2017Article
- Activation of FXR protects against renal fibrosis via suppressing Smad3 expression.Scientific reports · 2016Article
- Redox-sensitive MAPK and Notch3 regulate fibroblast differentiation and activation: a dual role of ERK1/2.Oncotarget · 2016Article
- miR-101 targeting ZFX suppresses tumor proliferation and metastasis by regulating the MAPK/Erk and Smad pathways in gallbladder carcinoma.Oncotarget · 2016Article
- HNF1 regulates critical processes in the human epididymis epithelium.Molecular and cellular endocrinology · 2016Article
- Deletion of the gene for adiponectin accelerates diabetic nephropathy in the Ins2 (+/C96Y) mouse.Diabetologia · 2015Article
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4 authors at 1 institution in 1 country.
Funding
Abstract
Transforming growth factor-β (TGF-β) signaling plays an important and complex role in renal fibrogenesis. The seemingly simple TGF-β/Smad cascade is intensively regulated at several levels, including crosstalk with other signaling pathways. Epidermal growth factor (EGF) is a potent mitogen for epithelial cells and is elevated in diseased kidneys. In this study, we examined its effect on TGF-β-induced fibrotic changes in human proximal tubular epithelial cells. Simultaneous treatment with EGF specifically inhibited basal and TGF-β-induced type-I collagen and α-smooth muscle actin (αSMA) expression at both mRNA and protein levels. These effects were prevented by inhibition of either the EGF receptor kinase or its downstream MEK kinase but not by blockade of either the JNK or PI3K pathway. Overexpression of a constitutively active MEK1 construct mimicked the inhibitory effect of EGF. Further, EGF suppressed Smad transcriptional activities, as shown by reduced activation of ARE-luc and SBE-luc. Both reductions were prevented by MEK inhibition. However, EGF did not block Smad2 or Smad3 phosphorylation by TGF-β, or Smad2/3 nuclear import. Finally EGF induced the phosphorylation and expression of TGIF, a known TGF-β/Smad repressor. Both the phosphorylation and the induction were blocked by a MEK inhibitor. Overexpression of TGIF abolished TGF-β-induced αSMA promoter activity. Together these results suggest that EGF inhibits two TGF-β-stimulated markers of EMT through EGF receptor tyrosine kinase and downstream ERK activation, but not through PI3K or JNK. The inhibition results from effector mechanisms downstream of Smads, and most likely involves the transcriptional repressor, TGIF.
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