TGF-β1-Induced Airway Smooth Muscle Cell Proliferation Involves TRPM7-Dependent Calcium Influx via TGFβR/SMAD3. (November 2018)

• Record Type: Journal Article
• Authors: Chen, Ming; Zhang, Wei; Shi, Jianting; Jiang, Shanping
• Is Part Of: Molecular immunology. Volume 103(2018:Nov.)
• Page Start: 173
• Page End: 181
• Publication Date: 2018-11
• Subjects: ASMCs airway smooth muscle cells -- BALF bronchoalveolar lavage fluid -- ROCC receptor-operated Ca2+ channels -- SMAD drosophila mothers against decapentaplegic protein -- SIS3 specific inhibitor of Smad3 -- SOCC store-operated Ca2+ channels -- [Ca2+]i intracellular Ca2+ concentration -- NC negative control -- OVA ovalbumin -- TGF-β1 transforming growth factor-β1 -- TGFβR transforming growth factor-β1 receptor -- TRPC transient receptor potential channel -- TRPM7 transient receptor potential melastatin 7; Asthma -- Airway smooth muscle cells -- TRPM7 -- TGF-β1 -- TGFβR/SMAD3; Immunochemistry -- Periodicals; Molecular biology -- Periodicals; Immunochemistry -- Periodicals; Allergy and Immunology -- Periodicals; Molecular Biology -- Periodicals; Immunochimie -- Périodiques; Biologie moléculaire -- Périodiques; Immunochemistry; Molecular biology; Periodicals; Electronic journals; 571.96
• DOI: 10.1016/j.molimm.2018.09.015
• Languages: English
• ISSNs: 0161-5890

Abstract

Highlights: TGF-β1 and TRPM7 expressed higher than those from control mice by time-dependent in asthmatic mice model with airway remodeling. TGF-β1 increases TRPM7 expression in ASMCs through TGFβR/Smad3 pathway. Knocking down TRPM7 decreases Ca 2+ influx, ASMCs proliferation and induces apoptosis. Abstract: Background: TRPM7 in mast cells plays a key role in asthma. However, the effect of TRPM7 on TGF-β1-induced airway smooth muscle cell (ASMC) proliferation remains unclear. Therefore, we designed this study to explore whether TRPM7 is involved in TGF-β1-induced ASMC proliferation. Methods: An asthmatic mouse model was established, and the expressions of TGF-β1 and TRPM7 in mice lungs were detected using enzyme-linked immunosorbent assay (ELISA) and western blotting. In addition, murine ASMCs were cultured and stimulated with TGF-β1. Possible TGF-β1 and TRPM7 interactions were examined using RT-PCR and western blotting analyses with ASMCs. The effect of TRPM7 knockdown on ASMC calcium influx was assessed by the fluorescent indicator indo-1. MTT and flow cytometry were applied to evaluate the effects of TRPM7 knockdown on ASMC proliferation and apoptosis. Results: TGF-β1 elevated the expression of TRPM7 via TGFβR/SMAD3. Knocking down TRPM7 decreased the intracellular Ca 2+ concentration and cellular proliferation of ASMCs, although apoptosis remained unaffected. Conclusions: Our initial findings suggest that TRPM7 inhibition may prevent asthma-induced airway remodeling.