Key result
Endothelin-1 significantly potentiated TGF-β1-induced endothelial-to-mesenchymal transition, increasing the proportion of cells expressing α-SMA from 27% to 52%.
Why the study?
Does ET-1 potentiate TGF-β1-induced endothelial-to-mesenchymal transition and tissue fibrosis in murine models?
Does ET-1 potentiate TGF-β1-induced endothelial-to-mesenchymal transition and tissue fibrosis in murine models?
Absolute Event Rate: 52% vs 27%
ET-1 potentiates TGF-β1-induced endothelial-to-mesenchymal transition and tissue fibrosis, suggesting a novel profibrotic mechanism for ET-1.
ET-1 may mediate TGF-β1-induced EndoMT in murine lung endothelium; leaves open its role in human fibrosis.
TGF-β-induced endothelial-to-mesenchymal transition (EndoMT) is a newly recognized source of profibrotic activated myofibroblasts and has been suggested to play a role in the pathogenesis of various fibrotic processes. Endothelin-1 (ET-1) has been implicated in the development of tissue fibrosis but its participation in TGF-β-induced EndoMT has not been studied. Here we evaluated the role of ET-1 on TGF-β1-induced EndoMT in immunopurified CD31+/CD102+ murine lung microvascular endothelial cells. The expression levels of α-smooth muscle actin (α-SMA), of relevant profibrotic genes, and of various transcription factors involved in the EndoMT process were assessed employing quantitative RT-PCR, immunofluorescence histology and Western blot analysis. TGF-β1 caused potent induction of EndoMT whereas ET-1 alone had a minimal effect. However, ET-1 potentiated TGF-β1-induced EndoMT and TGF-β1-stimulated expression of mesenchymal cell specific and profibrotic genes and proteins. ET-1 also induced expression of the TGF-β receptor 1 and 2 genes, suggesting a plausible autocrine mechanism to potentiate TGF-β-mediated EndoMT and fibrosis. Stimulation of TGF-β1-induced skin and lung fibrosis by ET-1 was confirmed in vivo in an animal model of TGF-β1-induced tissue fibrosis. These results suggest a novel role for ET-1 in the establishment and progression of tissue fibrosis.
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Wermuth et al. (2016) studied Tissue fibrosis. Endothelin-1 (ET-1) combined with TGF-β1 vs. TGF-β1 alone or saline was evaluated on Proportion of cells expressing α-SMA (EndoMT marker). Endothelin-1 significantly potentiated TGF-β1-induced endothelial-to-mesenchymal transition, increasing the proportion of cells expressing α-SMA from 27% to 52%.
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