{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T06:12:27Z","timestamp":1788502347804,"version":"build-2803163510"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Transforming Growth Factor-\u03b2 (TGF-\u03b2) has been implicated for its role in fibrosis and progression of chronic kidney disease (CKD) in both humans and rodents. Additionally, CKD is a common and progressive condition in canines, with striking pathological similarities to human disease. However, targeted therapies addressing fibrogenic mediators in dogs remain underexplored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We investigated the role of all three TGF-\u03b2 isoforms (TGF-\u03b21, TGF-\u03b22, and TGF-\u03b23) in CKD and renal fibrosis with\n                      <jats:italic>in vitro<\/jats:italic>\n                      model systems using human and canine primary renal proximal tubular epithelial cells. The studies assessed the induction of the canonical TGF-\u03b2 pathway and the ability of a novel canine anti-TGF-\u03b2 monoclonal antibody, cirevetmab, to neutralize these effects. All three TGF-\u03b2 isoforms induced phosphorylation of SMAD3 (homologs of Drosophila mothers against decapentaplegic and C. elegans SMA proteins), nuclear translocation, and alpha-smooth muscle actin (\u03b1SMA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Treatment with cirevetmab led to robust neutralization of TGF-\u03b21-induced SMAD phosphorylation and fibrotic marker changes. Notably, although cirevetmab exerted modest neutralization of TGF-\u03b23-induced SMAD phosphorylation, this was not associated with a significant change in TGF-\u03b23-induced fibrotic markers. Conversely, no neutralization of TGF-\u03b22-induced activity was observed with cirevetmab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      Our results demonstrate that cirevetmab selectively neutralizes TGF-\u03b21 and, to a lesser extent, TGF-\u03b23-induced SMAD phosphorylation\n                      <jats:italic>in vitro<\/jats:italic>\n                      , while only significantly neutralizing TGF-\u03b21-induced fibrotic markers in renal proximal tubule cells.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fvets.2026.1885917","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:28:59Z","timestamp":1788499739000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cirevetmab, a novel canine anti\u2013TGF\u03b2 monoclonal antibody, exerts antifibrotic effects on renal cells in vitro"],"prefix":"10.3389","volume":"13","author":[{"given":"Dayna L.","family":"Kappenman","sequence":"first","affiliation":[{"name":"Zoetis Inc., Global Therapeutics, Veterinary Medicine Research & Development","place":["Kalamazoo, MI, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher L.","family":"Koehler","sequence":"additional","affiliation":[{"name":"PhenoVista Biosciences","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reese N.","family":"Prentice","sequence":"additional","affiliation":[{"name":"PhenoVista Biosciences","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Koziar","sequence":"additional","affiliation":[{"name":"Zoetis Inc., Global Portfolio Marketing","place":["Parsippany, NJ, United 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