ALK-1 to ALK-5 ratio dictated by the Akt1-β-catenin pathway regulates TGFβ-induced endothelial-to-mesenchymal transition

Arti Verma, Sandeep Artham, Payaningal R Somanath
Gene 2020 November 3, : 145293
Endothelial-to-mesenchymal transition (EndMT) indispensable in embryogenesis also occurs in several human pathologies. Although transforming growth factor-β (TGFβ) has been demonstrated to induce EndMT, the type-I receptors (ALK-1 and ALK-5) responsible for TGFβ-induced EndMT is unclear. In the current study, we investigated the role of the Akt1 pathway in ALK1 and ALK5 expression regulation in response to TGFβ1 and TGFβ2 in human microvascular endothelial cells (HMECs). Whereas treatment with TGFβ1 and TGFβ2 or Akt1 gene silencing promoted EndMT accompanied by increased ALK5 expression and reduced ALK1 expression accompanied by increased expression of N-cadherin and reduced expression of eNOS in HMECs, treatment with ALK-5 inhibitor (SB431542) blunted these effects. Importantly, the inhibitor of β-catenin (ICG-001) suppressed TGFβ1- and TGFβ2-induced ALK5 expression in both normal and Akt1 deficient HMECs indicating the integral role of Akt1-β-catenin pathway in the regulation of ALK5 expression promoting EndMT.

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