ArticleFrontiers in cell and developmental biology2021
Bone Morphogenetic Protein Antagonist Gremlin-1 Increases Myofibroblast Transition in Dermal Fibroblasts: Implications for Systemic Sclerosis.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Grem1 inhibits osteogenic differentiation of MBMSCs in OVX rats through BMP/Smad1/5 signaling pathway.Regenerative therapy · 2025Article
- Evaluation of Gremlin-1 as a therapeutic target in metabolic dysfunction-associated steatohepatitis.eLife · 2024Article
- CXCL12+ dermal fibroblasts promote neutrophil recruitment and host defense by recognition of IL-17.The Journal of experimental medicine · 2024Article
- The Role of Myofibroblasts in Physiological and Pathological Tissue Repair.Cold Spring Harbor perspectives in biology · 2023Review
- Therapeutic effects of adipose-derived mesenchymal stem/stromal cells with enhanced migration ability and hepatocyte growth factor secretion by low-molecular-weight heparin treatment in bleomycin-induced mouse models of systemic sclerosis.Arthritis research & therapy · 2022Article
- A Comparative Analysis of the Wound Healing-Related Heterogeneity of Adipose-Derived Stem Cells Donors.Pharmaceutics · 2022Article
- Grem1 accelerates nucleus pulposus cell apoptosis and intervertebral disc degeneration by inhibiting TGF-β-mediated Smad2/3 phosphorylation.Experimental & molecular medicine · 2022Article
- HDAC5-mediated Smad7 silencing through MEF2A is critical for fibroblast activation and hypertrophic scar formation.International journal of biological sciences · 2022Article
- Gremlin: a complex molecule regulating wound healing and fibrosis.Cellular and molecular life sciences : CMLS · 2021Review
- Circulating Gremlin-1 is elevated in systemic sclerosis patients.Journal of scleroderma and related disorders · 2021Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSystemic Sclerosis is an autoimmune connective tissue disease which results in fibrosis of the skin and lungs. The disease is characterized by activation of myofibroblasts but what governs this is unknown. Gremlin-1 is a BMP antagonist that is developmentally regulated and we sought to investigate its role in Systemic Sclerosis.
methodsDermal fibroblasts were transfected with Grem1pcDNA3.1 expression vectors or empty vectors. Various markers of myofibroblasts were measured at the mRNA and protein levels. Scratch wound assays were also performed. Media Transfer experiments were performed to evaluate cytokine like effects. Various inhibitors of TGF-β signaling and MAPK signaling were used post-transfection. siRNA to Gremlin-1 in SSc dermal fibroblasts were performed to evaluate the role of Gremlin-1. Different cytokines were incubated with fibroblasts and Gremlin-1 measured. Bleomycin was used as model of fibrosis and immunohistochemistry performed.
resultsOverexpression of Gremlin-1 was achieved in primary dermal fibroblasts and lead to activation of quiescent cells to myofibroblasts indicated by collagen and α-Smooth muscle actin. Overexpression also led to functional effects. This was associated with increased TGF-β1 levels and SBE luciferase activity but not increased Thrombospondin-1 expression. Inhibition of Gremlin-1 overexpression cells with antibodies to TGF-β1 but not isotype controls led to reduced collagen and various TGF-β pathway chemical inhibitors also led to reduced collagen levels. In SSc cells siRNA mediated reduction of Gremlin-1 reduced collagen expression and CTGF gene and protein levels in these cells. IL-13 did not lead to elevated Gremlin-1 expression nor did IL-11. Gremlin-1 was elevated in an animal model of fibrosis compared to NaCl-treated mice.
conclusionGremlin-1 is a key regulator of myofibroblast transition leading to enhanced ECM deposition. Strategies that block Gremlin-1 maybe a possible therapeutic target in fibrotic diseases such as SSc.
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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 Socratic graph.