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Life Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Kidney fibrosis is a common manifestation of chronic kidney diseases, with parenchymal tissue scarring serving as a histologic predictor of functional deterioration. Considering the relationships between contact-phase system activation and renal fibrosis as well as potential direct profibrotic activities of factor XII (FXII), we hypothesized that FXII inhibition with an anti-FXII\/activated FXII (FXIIa) antibody (3F7) demonstrates therapeutic efficacy in a mouse model of unilateral ureteral obstruction (UUO). Treatment of UUO mice with 3F7 attenuated kidney fibrosis, as evidenced by preserved tissue structure, decreased deposition of collagen, and diminished apoptosis, but increased proliferation of tubular epithelial cells. No effect was observed with the administration of C1 esterase inhibitor, which serves as a primary plasma inhibitor of FXIIa and kallikrein. Transcriptome analysis revealed that 3F7 therapy predominantly affects stress-activated protein kinase signaling cascades and signal transduction in response to DNA damage. Exposure of renal epithelial cells to FXII or FXIIa triggered p21 expression in an Akt- and ERK1\/2-dependent manner. Accordingly, treatment of UUO mice with 3F7 reduced numbers of p21\n                    <jats:sup>+<\/jats:sup>\n                    renal tubular epithelial cells. Our work provides proof-of-concept data supporting efficacy of 3F7 in the UUO model and unravels molecular mechanisms underlying the protective role of FXII inhibition in chronic kidney injury.\n                  <\/jats:p>","DOI":"10.1007\/s00018-025-05988-z","type":"journal-article","created":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T21:18:18Z","timestamp":1764451098000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of FXIIa attenuates kidney fibrosis in mice with unilateral ureteral obstruction"],"prefix":"10.1007","volume":"83","author":[{"given":"Daniel","family":"Kalina","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Potaczek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinyang","family":"Zeng-Brouwers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Boehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc W.","family":"Nolte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Bielohuby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph T.","family":"Schermuly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liliana","family":"Schaefer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3656-2932","authenticated-orcid":false,"given":"Malgorzata","family":"Wygrecka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,29]]},"reference":[{"key":"5988_CR1","unstructured":"Centers for Disease Control and Prevention. 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