MiR-23b controls TGF-β1 induced airway smooth muscle cell proliferation via TGFβR2/p-Smad3 signals

Mol Immunol. 2016 Feb:70:84-93. doi: 10.1016/j.molimm.2015.12.012. Epub 2015 Dec 31.

Abstract

Background: Abnormal proliferation of ASM (airway smooth muscle) directly contributes to the airway remodeling during development of lung diseases such as asthma. Here we report that a specific microRNA (miR-23b) controls ASMCs proliferation through directly inhibiting TGFβR2/p-Smad3 pathway.

Methods: The expression of miR-23b in ASMCs was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and apoptosis of ASMCs were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated.

Results: Overexpression of miR-23b significantly inhibited TGF-β1-induced ASMCs proliferation and promoted apoptosis. RT-PCR and Western blotting analysis showed miR-23b negatively regulates the expression of TGFβR2 and p-Smad3 in ASMCs. Subsequent analyses demonstrated that TGFβR2 was a direct and functional target of miR-23b, which was validated by the dual luciferase reporter assay.

Conclusions: MiR-23b may function as an inhibitor of airway smooth muscle cells proliferation through inactivation of TGFβR2/p-Smad3 pathway.

Keywords: Airway smooth muscle cells; TGFβR2/p-Smad3; miR-23b.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Airway Remodeling / physiology*
  • Animals
  • Apoptosis / physiology
  • Asthma / metabolism
  • Blotting, Western
  • Cell Proliferation / physiology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / physiology*
  • Mice
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Myocytes, Smooth Muscle / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / metabolism
  • Real-Time Polymerase Chain Reaction
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Signal Transduction*
  • Smad3 Protein / metabolism
  • Transforming Growth Factor beta1 / metabolism*

Substances

  • MicroRNAs
  • Mirn23b microRNA, mouse
  • Receptors, Transforming Growth Factor beta
  • Smad3 Protein
  • Smad3 protein, mouse
  • Transforming Growth Factor beta1
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type II