TRPV1 attenuates epithelial-mesenchymal transition via calpain-protein tyrosine phosphatase pathway in lens epithelial cells

TRPV1, which is widely expressed throughout the body, is a non-selective cation channel activated by capsaicin. We previously reported that TRPV1 activation suppressed TGFβ2-induced epithelial-mesenchymal transition (EMT) by inhibiting Epidermal Growth Factor Receptor (EGFR) phosphorylation in lens epithelial cells (Sugiyama et al., 2021). However, the detailed molecular mechanism remains unclear. In this study, we focused on the calpain-protein tyrosine phosphatase (PTP) pathway to elucidate the detailed mechanism underlying TRPV1-induced EMT suppression. Calpain and PTP inhibitors mitigated the suppressive effect of capsaicin on TGFβ2-induced EMT in vitro and ex vivo. Finally, we shown that CalpainS1 and PTPN9 overexpression abrogated the effect of capsaicin on EMT in lens epithelial cells. Our findings indicate that calpain and PTP proteins are good candidates for preventing EMT after cataract surgery.