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Title: Matriptase activation of gq drives epithelial disruption and inflammation via RSK and DUOX
Authors: Ma, Jiajia
Scott, Claire A.
Ho, Ying Na
Mahabaleshwar, Harsha
Marsay, Katherine S.
Zhang, Changqing
Teow, Christopher Kj
Ng, Ser Sue
Zhang, Weibin
Tergaonkar, Vinay 
Partridge, Lynda J.
Roy, Sudipto 
Amaya, Enrique
Carney, Tom J.
Keywords: Epidermis
Hydrogen peroxide
Issue Date: 24-Jun-2021
Publisher: eLife Sciences Publications Ltd
Citation: Ma, Jiajia, Scott, Claire A., Ho, Ying Na, Mahabaleshwar, Harsha, Marsay, Katherine S., Zhang, Changqing, Teow, Christopher Kj, Ng, Ser Sue, Zhang, Weibin, Tergaonkar, Vinay, Partridge, Lynda J., Roy, Sudipto, Amaya, Enrique, Carney, Tom J. (2021-06-24). Matriptase activation of gq drives epithelial disruption and inflammation via RSK and DUOX. eLife 10 : e66596. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
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, NfkB 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 demonstrate that hai1a has elevated MAPK pathway activity, inhibition of which rescues the epidermal defects. Finally, we identify RSK kinases as MAPK targets disrupting adherens junctions in hai1a mutants. Our work maps novel signalling cascades mediating the potent effects of Matriptase on epithelia, with implications for tissue damage response and carcinoma progression. © 2021, eLife Sciences Publications Ltd. All rights reserved.
Source Title: eLife
ISSN: 2050-084X
DOI: 10.7554/elife.66596
Rights: Attribution 4.0 International
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