ArticleThe American journal of pathology2003
Hepatocyte growth factor suppresses renal interstitial myofibroblast activation and intercepts Smad signal transduction.
Article in The American journal of pathology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 148 citations in OpenAlex.
- Combinational Therapy of Mesenchymal Stem Cells and Metformin in Bleomycin-Induced Idiopathic Pulmonary Fibrosis in Rat Model.Applied biochemistry and biotechnology · 2025Article
- Inhibition and reversal of a TGF-β1 induced myofibroblast phenotype by adipose tissue-derived paracrine factors.Stem cell research & therapy · 2024Article
- Evaluation of CRISPR/Cas9 mediated TGIF gene editing to inhibit corneal fibrosis in vitro.Experimental eye research · 2022Article
- MSC secreted extracellular vesicles carrying TGF-beta upregulate Smad 6 expression and promote the regrowth of neurons in spinal cord injured rats.Stem cell reviews and reports · 2022Article
- The hepatocyte growth factor/c-met pathway is a key determinant of the fibrotic kidney local microenvironment.iScience · 2021Article
- The Mechanism of CD8Biomolecules · 2021Review
- Progress in drug delivery system for fibrosis therapy.Asian journal of pharmaceutical sciences · 2021Review
- Sonic hedgehog selectively promotes lymphangiogenesis after kidney injury through noncanonical pathway.American journal of physiology. Renal physiology · 2019Article
- Renoprotective effects of a novel cMet agonistic antibody on kidney fibrosis.Scientific reports · 2019Article
- Comparison of the Effects of Indobufen and Warfarin in a Rat Model of Adenine-Induced Chronic Kidney Disease.Medical science monitor : international medical journal of experimental and clinical research · 2019Article
- Gene Silencing via PDA/ERK2-siRNA-Mediated Electrospun Fibers for Peritendinous Antiadhesion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- MET/HGF Co-Targeting in Pancreatic Cancer: A Tool to Provide Insight into the Tumor/Stroma Crosstalk.International journal of molecular sciences · 2018Review
- Renal Injury during Long-Term Crizotinib Therapy.International journal of molecular sciences · 2018Article
- Hepatocyte Growth Factor Regulates the miR-206-HDAC4 Cascade to Control Neurogenic Muscle Atrophy following Surgical Denervation in Mice.Molecular therapy. Nucleic acids · 2018Article
- Soluble cMet levels in urine are a significant prognostic biomarker for diabetic nephropathy.Scientific reports · 2018Article
- GDF11 induces kidney fibrosis, renal cell epithelial-to-mesenchymal transition, and kidney dysfunction and failure.Surgery · 2018Article
- Effects of Platelet-Rich Plasma on Kidney Regeneration in Gentamicin-Induced Nephrotoxicity.Journal of Korean medical science · 2017Article
- Signaling Crosstalk between Tubular Epithelial Cells and Interstitial Fibroblasts after Kidney Injury.Kidney diseases (Basel, Switzerland) · 2016Review
- Ockham's razor for the MET-driven invasive growth linking idiopathic pulmonary fibrosis and cancer.Journal of translational medicine · 2016Review
- TGF-β: the master regulator of fibrosis.Nature reviews. Nephrology · 2016Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Interstitial myofibroblasts are alpha-smooth muscle actin-positive cells that play a crucial role in the accumulation of excess extracellular matrix during renal interstitial fibrogenesis. Despite their importance in the pathogenesis of renal fibrosis, relatively little is known about the regulators and the mechanism controlling the activation of renal interstitial myofibroblasts in disease conditions. Here, we show that hepatocyte growth factor (HGF) acts as a potent inhibitor of the transforming growth factor (TGF)-beta1-mediated myofibroblastic activation from normal rat renal interstitial fibroblasts (NRK-49F). Simultaneous incubation of HGF abolished TGF-beta1-induced de novo alpha-smooth muscle actin expression, F-actin reorganization, and interstitial collagen I overproduction in a dose-dependent manner. To decipher the mechanism underlying HGF antagonizing TGF-beta1's action, we examined the effects of HGF on TGF-beta1-mediated Smad signaling. HGF neither inhibited Smad-2/3 phosphorylation and their association with Smad-4 induced by TGF-beta1, nor significantly affected inhibitory Smad-6 and -7 expression and cellular abundance of Smad transcriptional co-repressors in NRK-49F cells. However, pretreatment with HGF markedly attenuated activated Smad-2/3 nuclear translocation and accumulation. This action of HGF was apparently dependent on HGF-mediated extracellular signal-regulated kinase-1 and -2 (Erk-1/2) phosphorylation and activation. Inhibition of Erk-1/2 activation by Mek kinase inhibitor PD98059 restored TGF-beta1-mediated Smad-2/3 nuclear accumulation and myofibroblast activation. In vivo, HGF selectively blocked Smad-2/3 nuclear accumulation in renal interstitial cells in the fibrotic kidneys induced by unilateral ureteral obstruction. Therefore, HGF suppresses TGF-beta1-mediated renal interstitial myofibroblastic activation; and this action of HGF is likely related to a mitogen-activated protein kinase-dependent blockade of Smad nuclear translocation.
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Registered trials
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.