Mechanical stress-induced mast cell degranulation activates TGF-β1 signalling pathway in pulmonary fibrosis

Thorax
Chiko ShimboriMartin Kolb

Abstract

The role of mast cells accumulating in idiopathic pulmonary fibrosis (IPF) lungs is unknown. We investigated the effect of fibrotic extracellular matrix (ECM) on mast cells in experimental and human pulmonary fibrosis. In IPF lungs, mast cell numbers were increased and correlated with disease severity (control vs 60%<FVC<90%, mean difference=-222.7, 95% CI -386.3 to -59.2, p=0.004; control vs FVC<60%, mean difference=-301.7, 95% CI of difference -474.1 to -129.34, p=0.0001; FVC>90% vs 60%<FVC<90%, mean difference=-189.6, 95% CI of difference -353.1 to -26.03, p=0.017; FVC>90% vs FVC<60%, mean difference=-268.6, 95% CI of difference -441.0 to -96.17, p=0.0007). Plasma tryptase levels were increased in IPF and negatively correlated with FVC (control vs FVC<60%, mean difference=-17.12, 95% CI of difference -30.02 to -4.22, p=0.006: correlation curves R=-0.045, p=0.025). In a transforming growth factor (TGF)-β1-induced pulmonary fibrosis model, chymase-positive and tryptase-positive mast cells accumulated in fibrotic lung. Lung tissue was decellularised and reseeded with bone marrow or peritoneum-derived mast cells; cells on fibrotic ECM released more TGF-β1 compared with normal ECM (active TGF-β1: bone marrow-derived mast cell (BM...Continue Reading

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Citations

Aug 1, 2019·Current Opinion in Supportive and Palliative Care·Mirjam J G van Manen, Marlies S Wijsenbeek
Mar 4, 2020·American Journal of Respiratory and Critical Care Medicine·Leigh M CaginoRobert P Dickson
Jun 9, 2020·Inflammatory Bowel Diseases·Bin LiuJi-Yu Li
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Dec 4, 2019·Endocrine, Metabolic & Immune Disorders Drug Targets·Thea MagroneEmilio Jirillo
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Jan 10, 2021·International Journal of Molecular Sciences·Mariam BagherGunilla Westergren-Thorsson
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Mar 17, 2021·Cell Death Discovery·Yi Xin SheXiao Xiao Tang
Apr 27, 2021·Journal of Alzheimer's Disease : JAD·Vince SzegeczkiTamás Juhász

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