Cx43 upregulation in HUVECs under stretch via TGF-β1 and cytoskeletal network

Yumeng Shi, Xinbo Li, Jin Yang

Research output: Contribution to journalArticlepeer-review

Abstract

Many physiological and pathophysiological processes in cells or tissues are involved in mechanical stretch, which induces the gap junction gene expression and cytokine TGF beta changes. However, the underlying mechanisms of the gap junction gene expression remain unknown. Here, we showed that the mRNA and protein levels of Cx43 in human umbilical vein endothelial cells (HUVECs) were significantly increased after 24 h stretch stimulation, and TGF beta1 (not TGF beta2) expression was also upregulated. Administration of TGF beta1 into HUVECs without stretch also induced upregulation of Cx43 expression. However, SB431542, a specific inhibitor of the TGF beta1 receptor, blocked the Cx43 protein upregulation caused by TGF beta1. Further, the increase of Cx43 protein expression under the stretch condition was partially blocked by SB431542; it was also partially blocked by simultaneous administration of anti-TGF beta1 monoclonal neutralization antibody. Importantly, the upregulation of Cx43 induced by stretch was blocked by the administration of actin and microtubule inhibitors, while NEDD4, a key element in mediating Cx43 protein ubiquitination and degradation, was not changed under the stretch condition. In conclusion, upregulation of Cx43 expression under the 24 h stretch condition is mediated via TGF beta1 receptor signaling pathway, and it also involves the actin and microtubule cytoskeletal network.

Original languageEnglish (US)
Pages (from-to)463-474
Number of pages12
JournalOpen Medicine (Poland)
Volume17
Issue number1
DOIs
StatePublished - Jan 1 2022
Externally publishedYes

Keywords

  • actin
  • connexin43
  • gap junction
  • mechanical stretch
  • TGF beta1

ASJC Scopus subject areas

  • Medicine(all)

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