Matriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX.

ABSTRACT: Epithelial tissues are primed to respond to insults by activating epithelial cell motility and rapid inflammation. Such responses are also elicited upon overexpression of the membrane-bound protease, Matriptase, or mutation of its inhibitor, Hai1. Unrestricted Matriptase activity also predisposes to carcinoma. How Matriptase leads to these cellular outcomes is unknown. We demonstrate that zebrafish hai1a mutants show increased H₂O₂, NfκB signalling, and IP₃R -mediated calcium flashes, and that these promote inflammation, but do not generate epithelial cell motility. In contrast, inhibition of the Gq subunit in hai1a mutants rescues both the inflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demon

SUBMITTER: Ma J 

PROVIDER: S-EPMC8291973 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature