ArticleBioMed research international2014
Gremlin activates the Smad pathway linked to epithelial mesenchymal transdifferentiation in cultured tubular epithelial cells.
Article in BioMed research international, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 58 citations in OpenAlex.
- Exploring the Cellular and Molecular Landscape of Idiopathic Pulmonary Fibrosis: Integrative Multi-Omics and Single-Cell Analysis.Biomedicines · 2025Article
- Mesenchymal Stem Cells Mediated Suppression of GREM2 Inhibits Renal Epithelial-Mesenchymal Transition and Attenuates the Progression of Diabetic Kidney Disease.International journal of stem cells · 2025Article
- Biomarkers in ANCA associated vasculitis: clinical utility, pitfalls and their role in the outcomes assessment.Frontiers in immunology · 2025Review
- PI3K/AKT signaling pathway as a critical regulator of epithelial-mesenchymal transition in colorectal tumor cells.Cell communication and signaling : CCS · 2023Review
- Cotransplantation of marginal mass allogeneic islets with 3D culture-derived adult human skin cells improves glycemia in diabetic mice.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2023Article
- GREM1/PPP2R3A expression in heterogeneous fibroblasts initiates pulmonary fibrosis.Cell & bioscience · 2022Article
- Gremlin-1 Promotes Colorectal Cancer Cell Metastasis by Activating ATF6 and Inhibiting ATF4 Pathways.Cells · 2022Article
- The interplay of fibroblasts, the extracellular matrix, and inflammation in scar formation.The Journal of biological chemistry · 2022Review
- Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Gremlin: a complex molecule regulating wound healing and fibrosis.Cellular and molecular life sciences : CMLS · 2021Review
- αVβ8 integrin targeting to prevent posterior capsular opacification.JCI insight · 2021Article
- Article
- Saikosaponin D Inhibits Peritoneal Fibrosis in Rats With Renal Failure by Regulation of TGFβ1/ BMP7 / Gremlin1/ Smad Pathway.Frontiers in pharmacology · 2021Article
- Gremlin-1 Promotes Metastasis of Breast Cancer Cells by Activating STAT3-MMP13 Signaling Pathway.International journal of molecular sciences · 2020Article
- Gremlin-1 augments the oestrogen-related receptor α signalling through EGFR activation: implications for the progression of breast cancer.British journal of cancer · 2020Article
- Extracellular BMP Antagonists, Multifaceted Orchestrators in the Tumor and Its Microenvironment.International journal of molecular sciences · 2020Review
- DHA inhibits Gremlin-1-induced epithelial-to-mesenchymal transition via ERK suppression in human breast cancer cells.Bioscience reports · 2020Article
- VEGFR2 Blockade Improves Renal Damage in an Experimental Model of Type 2 Diabetic Nephropathy.Journal of clinical medicine · 2020Article
- Asiaticoside inhibits TGF-β1-induced mesothelial-mesenchymal transition and oxidative stress via the Nrf2/HO-1 signaling pathway in the human peritoneal mesothelial cell line HMrSV5.Cellular & molecular biology letters · 2020Article
- No evidence of Gremlin1-mediated activation of VEGFR2 signaling in endothelial cells.The Journal of biological chemistry · 2019Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gremlin is a developmental gene upregulated in human chronic kidney disease and in renal cells in response to transforming growth factor-β (TGF-β). Epithelial mesenchymal transition (EMT) is one process involved in renal fibrosis. In tubular epithelial cells we have recently described that Gremlin induces EMT and acts as a downstream TGF-β mediator. Our aim was to investigate whether Gremlin participates in EMT by the regulation of the Smad pathway. Stimulation of human tubular epithelial cells (HK2) with Gremlin caused an early activation of the Smad signaling pathway (Smad 2/3 phosphorylation, nuclear translocation, and Smad-dependent gene transcription). The blockade of TGF-β, by a neutralizing antibody against active TGF-β, did not modify Gremlin-induced early Smad activation. These data show that Gremlin directly, by a TGF-β independent process, activates the Smad pathway. In tubular epithelial cells long-term incubation with Gremlin increased TGF-β production and caused a sustained Smad activation and a phenotype conversion into myofibroblasts-like cells. Smad 7 overexpression, which blocks Smad 2/3 activation, diminished EMT changes observed in Gremlin-transfected tubuloepithelial cells. TGF-β neutralization also diminished Gremlin-induced EMT changes. In conclusion, we propose that Gremlin could participate in renal fibrosis by inducing EMT in tubular epithelial cells through activation of Smad pathway and induction of TGF-β.
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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 Socratic graph.