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• W2904630591 endingPage "152" @default.
• W2904630591 startingPage "139" @default.
• W2904630591 abstract "The implantation of biomaterials into soft tissue leads to the development of foreign body response, a non-specific inflammatory condition that is characterized by the presence of fibrotic tissue. Epithelial-mesenchymal transition (EMT) is a key event in development, fibrosis, and oncogenesis. Emerging data support a role for both a mechanical signal and a biochemical signal in EMT. We hypothesized that transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive channel, is a mediator of EMT.Normal human primary epidermal keratinocytes (NHEKs) were seeded on collagen-coated plastic plates or varied stiffness polyacrylamide gels in the presence or absence of TGFβ1, Immunofluorescence, immunoblot, and polymerase chain reaction analysis were performed to determine expression level of EMT markers and signaling proteins. Knock-down of TRPV4 function was achieved by siRNA transfection or by GSK2193874 treatment.We found that knock-down of TRPV4 blocked both matrix stiffness- and TGFβ1-induced EMT in NHEKs. In a murine skin fibrosis model, TRPV4 deletion resulted in decreased expression of the mesenchymal marker, α-SMA, and increased expression of epithelial marker, E-cadherin. Mechanistically, our data showed that: i) TRPV4 was essential for the nuclear translocation of TAZ in response to matrix stiffness and TGFβ1; ii) Antagonism of TRPV4 inhibited both matrix stiffness-induced and TGFβ1-induced expression of TAZ proteins; and iii) TRPV4 antagonism suppressed both matrix stiffness-induced and TGFβ1-induced activation of Smad2/3, but not of AKT.These data identify a novel role for TRPV4-TAZ mechanotransduction signaling axis in regulating EMT in NHEKs in response to both matrix stiffness and TGFβ1." @default.
• W2904630591 created "2018-12-22" @default.
• W2904630591 creator A5061783001 @default.
• W2904630591 creator A5067309940 @default.
• W2904630591 creator A5087912513 @default.
• W2904630591 date "2018-12-11" @default.
• W2904630591 modified "2023-09-24" @default.
• W2904630591 title "The TRPV4-TAZ Mechanotransduction Signaling Axis in Matrix Stiffness- and TGFβ1-Induced Epithelial-Mesenchymal Transition" @default.
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