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MYH9 Inhibition Suppresses TGF-β1-Stimulated Lung Fibroblast-to-Myofibroblast Differentiation

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Previous cDNA microarray results showed that MYH9 gene expression levels are increased in TGF-β1-stimulated lung fibroblast. Recently, our proteomic results revealed that the expression levels of MYH9 protein are notably… Click to show full abstract

Previous cDNA microarray results showed that MYH9 gene expression levels are increased in TGF-β1-stimulated lung fibroblast. Recently, our proteomic results revealed that the expression levels of MYH9 protein are notably upregulated in lung tissues of bleomycin-treated rats. However, whether MYH9 plays a critical role in the differentiation of fibroblast remains unclear. Herein, we demonstrated that TGF-β1 increased MYH9 expression, and siRNA-mediated knockdown of MYH9 and pharmacological inhibition of MYH9 ATPase activity remarkably repressed TGF-β1-induced lung fibroblast-to-myofibroblast differentiation. TGF-β1-stimulated MYH9 induction might be via ALK5/Smad2/3 pathway but not through noncanonical pathways, including p38 mitogen-activated kinase, and Akt pathways in lung fibroblasts. Our results showed that MYH9 inhibition suppressed TGF-β1-induced lung fibroblast-to-myofibroblast differentiation, which provides valuable information for illuminating the pathological mechanisms of lung fibroblast differentiation, and gives clues for finding new potential target for pulmonary fibrosis treatment.

Keywords: lung; lung fibroblast; differentiation; tgf stimulated; fibroblast myofibroblast

Journal Title: Frontiers in Pharmacology
Year Published: 2020

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