Dataset Information

ERK1/2 drives IL-1?-induced expression of TGF-?1 and BMP-2 in torn tendons.

ABSTRACT: Diseased and injured tendons develop fibrosis, driven by factors including TGF-?, BMPs and CTGF. IL-1? and its signal transducer Erk1/2 are known to regulate TGF-? expression in animal tendons. We utilised tissues and cells isolated from patients with shoulder tendon tears and tendons of healthy volunteers to advance understanding of how inflammation induces fibrosis in diseased human tendons. ERK1/2 expression was reduced in torn (diseased) compared to healthy patient tendon tissues. We next investigated the fibrotic responses of tendon-derived cells isolated from healthy and diseased human tendon tissues in an inflammatory milieu. IL-1? treatment induced profound ERK1/2 signalling, TGFB1 and BMP2 mRNA expression in diseased compared to healthy tendon-derived cells. In the diseased cells, the ERK1/2 inhibitor (PD98059) completely blocked the IL-1?-induced TGFB1 and partially reduced BMP2 mRNA expression. Conversely, the same treatment of healthy cells did not modulate IL-1?-induced TGFB1 or BMP2 mRNA expression. ERK1/2 inhibition did not attenuate IL-1?-induced CTGF mRNA expression in healthy or diseased tendon cells. These findings highlight differences between ERK1/2 signalling pathway activation and expression of TGF-?1 and BMP-2 between healthy and diseased tendon tissues and cells, advancing understanding of inflammation induced fibrosis during the development of human tendon disease and subsequent repair.

SUBMITTER: Morita W

PROVIDER: S-EPMC6908634 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Publications

ERK1/2 drives IL-1β-induced expression of TGF-β1 and BMP-2 in torn tendons.

Morita Wataru W Snelling Sarah J B SJB Wheway Kim K Watkins Bridget B Appleton Louise L Carr Andrew J AJ Dakin Stephanie G SG

Scientific reports 20191212 1

Diseased and injured tendons develop fibrosis, driven by factors including TGF-β, BMPs and CTGF. IL-1β and its signal transducer Erk1/2 are known to regulate TGF-β expression in animal tendons. We utilised tissues and cells isolated from patients with shoulder tendon tears and tendons of healthy volunteers to advance understanding of how inflammation induces fibrosis in diseased human tendons. ERK1/2 expression was reduced in torn (diseased) compared to healthy patient tendon tissues. We next in ...[more]

PMID: 31831776

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Project description:Hydroxysafflor yellow A (HSYA) is an active ingredient of Carthamus tinctorius L.. This study aimed to evaluate the effects of HSYA on transforming growth factor-β1 (TGF-β1)-induced changes in proliferation, migration, differentiation, and extracellular matrix accumulation and degradation in human fetal lung fibroblasts (MRC-5), to explore the mechanisms whereby HSYA may alleviate pulmonary fibrosis. MRC-5 cells were incubated with various doses of HSYA and/or the TGF-β receptor type I kinase inhibitor SB431542 and then stimulated with TGF-β1. Cell proliferation was measured by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfo-phenyl)-2H-tetrazolium inner salt assay. Cell migration was detected by wound-healing assay. Protein levels of α-smooth muscle actin (α-SMA), collagen I α 1 (COL1A1), and fibronectin (FN) were measured by immunofluorescence. Protein levels of matrix metalloproteinase-2, tissue inhibitor of matrix metalloproteinase-1, tissue inhibitor of matrix metalloproteinase-2, TGF-β type II receptor (TβRII), and TGF-β type I receptor were detected by western blotting. TβRII knockdown with siRNA interfered with the inhibitory effect of HSYA on α-SMA, COL1A1, and FN expression, and TGF-β1-induced Sma and Mad protein (Smad), and extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway activation. The antagonistic effect of HSYA on the binding of fluorescein isothiocyanate-TGF-β1 to MRC-5 cell cytoplasmic receptors was measured by flow cytometry. HSYA significantly suppressed TGF-β1-induced cell proliferation and migration. HSYA could antagonize the binding of FITC-TGF-β1 to MRC-5 cell cytoplasmic receptors. Also HSYA inhibited TGF-β1-activated cell expression of α-SMA, COL1A1, and FN and phosphorylation level of Smad2, Smad3, and ERK by targeting TβRII in MRC-5 cells. These findings suggest that TβRII might be the target responsible for the inhibitory effects of HSYA on TGF-β1-induced pathological changes in pulmonary fibrosis.

Dataset Information

ERK1/2 drives IL-1?-induced expression of TGF-?1 and BMP-2 in torn tendons.

Publications

ERK1/2 drives IL-1β-induced expression of TGF-β1 and BMP-2 in torn tendons.

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