TGF-β1-Induced Airway Smooth Muscle Cell Proliferation Involves TRPM7-Dependent Calcium Influx via TGFβR/SMAD3

Mol Immunol. 2018 Nov:103:173-181. doi: 10.1016/j.molimm.2018.09.015. Epub 2018 Oct 2.

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 Ca2+ concentration and cellular proliferation of ASMCs, although apoptosis remained unaffected.

Conclusions: Our initial findings suggest that TRPM7 inhibition may prevent asthma-induced airway remodeling.

Keywords: Airway smooth muscle cells; Asthma; TGF-β1; TGFβR/SMAD3; TRPM7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Female
  • Gene Expression Regulation / drug effects
  • Ion Transport / drug effects
  • Mice, Inbred BALB C
  • Myocytes, Smooth Muscle / drug effects*
  • Myocytes, Smooth Muscle / metabolism
  • RNA Interference
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Respiratory System / cytology
  • Signal Transduction / drug effects
  • Smad3 Protein / metabolism*
  • TRPM Cation Channels / genetics
  • TRPM Cation Channels / metabolism*
  • Transforming Growth Factor beta1 / metabolism
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • Receptors, Transforming Growth Factor beta
  • Smad3 Protein
  • TRPM Cation Channels
  • Transforming Growth Factor beta1
  • Trpm7 protein, mouse
  • Calcium