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Shaik O. Rahaman

Shaik O. Rahaman

University of Maryland, USA

Title: TRPV4 channels regulates matrix stiffness and TGFβ1-induced epithelial-mesenchymal transition

Biography

Biography: Shaik O. Rahaman

Abstract

Epithelial-mesenchymal transition (EMT) has critical functions in cellular processes including development, tissue healing, and oncogenesis. Emerging data support a role for both a mechanical signal, and a biochemical signal, in EMT. We report evidence showing that transient receptor potential vanilloid 4 (TRPV4) channel, is the likely mediator of EMT in response to both transforming growth factor β1 (TGFβ1), and matrix stiffness. We found that: i) genetic deficiency of TRPV4 channel blocked TGFβ1-induced EMT in normal mouse primary epidermal keratinocytes (NMEKs) as determined by changes in morphology and alterations of expression of EMT markers including E-cadherin (ECAD), N-cadherin (NCAD), and α-smooth muscle actin (α-SMA); and ii) TRPV4 deficiency prevented matrix stiffness-induced EMT in NMEKs. Intriguingly, TRPV4 deficiency in mice suppressed expression of mesenchymal markers, NCAD and α-SMA, in murine dermal fibrosis model. We found an increased co-localization of TRPV4 with NCAD, and decreased co-localization of TRPV4 with epithelial marker ECAD in skin tissues of bleomycin-treated wild-type mice compared to saline controls. Mechanistically, our results showed that: i) TRPV4 was critical for the nuclear translocation of YAP/TAZ (Yes-associated protein/transcriptional coactivator with PDZ- binding motif) in response to matrix stiffness and TGFβ1, ii) TRPV4 deletion inhibited both matrix stiffness- and TGFβ1- induced expression of YAP/TAZ proteins, and iii) TRPV4 deletion abrogated both matrix stiffness- and TGFβ1-induced activation of AKT, but not Smad2/3. Altogether, these data identify a novel role for TRPV4 in regulating EMT.