biostudies-literatureMa JMinistry of Education - Singaporee66596https://www.ebi.ac.uk/biostudies/studies/S-EPMC8291973biostudies-literatureUnknown10Epithelial 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 <i>hai1a</i> 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 <i>hai1a</i> mutants rescues both the inflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demoneLifeMatriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX.PMC82919732015-T1-001-035MOE2016-T3-1-005Marsay KSAmaya EHo YNZhang WMahabaleshwar HPartridge LJScott CACarney TJTergaonkar VTeow CKRoy SMa JZhang CNg SSfalseMatriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX.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 <i>hai1a</i> 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 <i>hai1a</i> mutants rescues both the inflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demon2021-01-01T00:00:00Z2021 Jun2026-06-11T04:04:22.86Z2022-02-10T22:15:56.317ZS-EPMC82919733416508110.7554/eLife.66596