Fibulin-5 promotes airway smooth muscle cell proliferation and migration via modulating Hippo-YAP/TAZ pathway

Biochem Biophys Res Commun. 2017 Nov 18;493(2):985-991. doi: 10.1016/j.bbrc.2017.09.105. Epub 2017 Sep 20.

Abstract

Asthma is a common chronic disease mainly occurs from childhood. Increased airway smooth muscle mass is involved in the pathogenesis of asthma. Fibulin-5 was upregulated in the lung tissues of patients with COPD and idiopathic pulmonary fibrosis. This study aimed to investigate Fibulin-5 expression in asthmatic patients and the effect and mechanism of Fibulin-5 on the proliferation and migration of airway smooth muscle cells (ASMCs). The expression of Fibulin-5, YAP, and TAZ in the induced sputum of 38 asthmatic children (19 mild and 19 moderate asthmatics) and 19 healthy controls was determined. The effects and mechanisms of Fibulin-5 on the proliferation and migration of ASMCs were analyzed through upregulating Fibulin-5. We found compared with healthy controls, the expression of Fibulin-5, YAP, and TAZ was increased in the induced sputum of asthmatic children and much higher in moderate asthmatics. Fibulin-5 overexpression promoted the proliferation and migration of ASMCs, upregulated the expression of YAP and TAZ, and reduced the levels of p-YAP and p-TAZ. YAP inhibitor (Peptide 17) abrogated the proliferation and migration of ASMCs induced by Fibulin-5 overexpression in a dose-dependent manner. Additionally, Fibulin-5 overexpression enhanced its binding capacity of β1 integrin, and β1 integrin blocking antibody partly reversed the effect of Fibulin-5 overexpression on the levels of YAP and TAZ. In conclusion, Fibulin-5 expression is correlated with the pathogenesis of childhood asthma. It may function at least partly through binding to β1 integrin and modulating Hippo-YAP/TAZ pathway to promote the proliferation and migration of ASMCs.

Keywords: Airway smooth muscle cell; Asthma; Fibulin-5; Hippo-YAP/TAZ pathway; β1 integrin.

MeSH terms

  • Adaptor Proteins, Signal Transducing / analysis
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adolescent
  • Airway Remodeling
  • Animals
  • Asthma / genetics
  • Asthma / metabolism*
  • Asthma / pathology
  • Cell Movement
  • Cell Proliferation
  • Cells, Cultured
  • Child
  • Extracellular Matrix Proteins / analysis
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / analysis
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Male
  • Mice, Inbred C57BL
  • Myocytes, Smooth Muscle / cytology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • Phosphoproteins / analysis
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / analysis
  • Protein-Serine-Threonine Kinases / metabolism*
  • Recombinant Proteins / analysis
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism*
  • Signal Transduction
  • Sputum / metabolism
  • Trans-Activators
  • Transcription Factors
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • Extracellular Matrix Proteins
  • FBLN5 protein, human
  • Fbln5 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Phosphoproteins
  • Recombinant Proteins
  • Trans-Activators
  • Transcription Factors
  • WWTR1 protein, human
  • YAP1 protein, human
  • Hippo protein, human
  • Protein-Serine-Threonine Kinases