Integrin-α7 signaling regulates connexin 43, M-cadherin, and myoblast fusion

Michael J. McClure, Allison N. Ramey, Mashaba Rashid, Barbara D. Boyan, Zvi Schwartz

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Integrin-α7 signaling regulates connexin 43, M-cadherin, and myoblast fusion. Am J Physiol Cell Physiol 316: C876 –C887, 2019. First published March 20, 2019; doi:10.1152/ajpcell.00282.2018.—Regen-erative medicine treatments for severe skeletal muscle injuries are limited, resulting in persistent functional deficits. Clinical options include neglecting the wound with the expectation that fibrosis will develop or using an autologous muscle graft with minimal functional improvement. A regenerative matrix can be used, but muscle fiber development on these matrices remains a challenge in vivo. Here, we explored the fundamental mechanisms that mediate cell-substrate signaling and its effect on cell-cell communication during myoblast fusion and tube formation to improve outcomes following implantation of matrices used to stimulate muscle regeneration. We previously reported that integrin-α7 was increased on anisotropic biomaterials, suggesting a role for α7β1 signaling in myoblast communication via connexin 43 and M-cadherin. Our results demonstrated that α7 silencing blocked expression of myogenic differentiation factor 1 (Myod), myogenin (Myog), myogenic factor 6 (Myf6), myosin heavy chain type 1 (Myh1), and transmembrane protein 8c (Tmem8c), indicating that myoblast fusion was inhibited. Expression of α5 and M-cadherin decreased but β1 and connexin 43 increased. We examined protein production and observed reduced extracellular-signal regulated kinase 1/2 (ERK) in α7-silenced cells that correlated with upregulation of connexin 43 and M-cadherin, suggesting a compensatory pathway. These results indicate that α7 signaling plays a critical role in ex vivo fusion and implicates a relationship with connexin 43 and M-cadherin.

Original languageEnglish (US)
Pages (from-to)C876-C887
JournalAmerican Journal of Physiology - Cell Physiology
Volume316
Issue number6
DOIs
StatePublished - Jun 2019

Keywords

  • Connexins
  • Integrins
  • M-cadherin
  • Muscle
  • Myoblast fusion

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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