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This protease activated matrix metalloproteases (MMPs) and degraded extracellular matrix. Other serine proteases are implicated in these mechanisms like kallikreins (KLKs). In this study, we identified for the first time that TFPI-2 is a potent inhibitor of KLK5 and 12. Computer modeling showed that the first Kunitz domain of TFPI-2 could interact with residues of KLK12 near the catalytic triad. Furthermore, like plasmin, KLK12 was able to activate proMMP-1 and -3, with no effect on proMMP-9. Thus, the inhibition of KLK12 by TFPI-2 greatly reduced the cascade activation of these MMPs and the cleavage of cysteine-rich 61, a matrix signaling protein. Moreover, when TFPI-2 bound to extracellular matrix, its classical localisation, the KLK12 inhibition was retained. Finally, TFPI-2 was downregulated in human non-small-cell lung tumour tissue as compared with non-affected lung tissue. These data suggest that TFPI-2 is a potent inhibitor of KLK12 and could regulate matrix remodeling and cancer progression mediated by KLK12.<\/jats:p>","DOI":"10.1515\/hsz-2020-0389","type":"journal-article","created":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T05:23:55Z","timestamp":1620797035000},"page":"1257-1268","source":"Crossref","is-referenced-by-count":14,"title":["Tissue factor pathway inhibitor 2 is a potent kallikrein-related protease 12 inhibitor"],"prefix":"10.1515","volume":"402","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1337-1121","authenticated-orcid":false,"given":"Marion","family":"Lavergne","sequence":"first","affiliation":[{"name":"Universit\u00e9 de Tours , F-37032 Tours , France"},{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Guillon-Munos","sequence":"additional","affiliation":[{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"},{"name":"Groupe IMT, Bio3 Institute , 15 rue du Plat D\u2019Etain, F-37020 Tours Cedex 1 , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Woodys","family":"Lenga Ma Bonda","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours , F-37032 Tours , France"},{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Attucci","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours , F-37032 Tours , France"},{"name":"INSERM, Imagerie et Cerveau (iBrain) , UMR 1253, F-37000 Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kryza","sequence":"additional","affiliation":[{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"},{"name":"Mater Research Institute, The University of Queensland , Woollongabba Brisbane , QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lia","family":"Barascu","sequence":"additional","affiliation":[{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"},{"name":"UMR 8226-CNRS\/UPMC, Institut de Biologie Physico-chimique, Sorbonne Universit\u00e9 , 13 rue Pierre et Marie Curie, F-75005 Paris , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Moreau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours , F-37032 Tours , France"},{"name":"INRA, UMR INRA 0083 - Biologie des Oiseaux et Aviculture (BOA) , F-37380 Nouzilly , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Petit-Courty","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours , F-37032 Tours , France"},{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damien","family":"Sizaret","sequence":"additional","affiliation":[{"name":"D\u00e9partement d\u2019Anatomie et Cytologie Pathologiques , H\u00f4pital Trousseau , CHRU de Tours, F-37044 Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yves","family":"Courty","sequence":"additional","affiliation":[{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Iochmann","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours , F-37032 Tours , France"},{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"},{"name":"Institut Universitaire de Technologie , F-37082 Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascale","family":"Reverdiau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Tours , F-37032 Tours , France"},{"name":"INSERM, Centre d\u2019Etude des Pathologies Respiratoires (CEPR) , UMR 1100, 10 boulevard Tonnell\u00e9, F-37032 Tours , France"},{"name":"Institut Universitaire de Technologie , F-37082 Tours , France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"2026041716170334800_j_hsz-2020-0389_ref_001","doi-asserted-by":"crossref","unstructured":"Bieth, J.G. 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