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Indoleamine\u20102,3\u2010dioxygenase and its downstream metabolites, kynurenines (KYNs), modulate immune response and may contribute to tissue protection in inflammatory conditions. This study aimed to investigate the potential antifibrotic effects of KYN and kynurenic acid (KYNA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>The effects of KYN and KYNA were investigated in fibroblast culture and in a rat model of unilateral ureteral obstruction\u2010induced renal fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      , both KYN and KYNA effectively inhibited TGF\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010mediated fibrotic signalling. KYNA suppressed collagen I expression and myofibroblast transdifferentiation. In a rat model of unilateral ureteral obstruction, KYNA reduced fibrotic area,\n                      <jats:italic>\u03b1<\/jats:italic>\n                      \u2010SMA\u2010positive regions as well as distal tubular dilatation in cortex and outer medulla. These reno\u2010protective effects were associated primarily with inhibition of the noncanonical TGF\n                      <jats:italic>\u03b2<\/jats:italic>\n                      pathway (pp38, pJNK\/JNK) and modulation of the Wnt\/\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u2010catenin and JAK2\/STAT3 pathways. Furthermore, KYNA influenced proinflammatory NF\u2010\n                      <jats:italic>\u03ba<\/jats:italic>\n                      B p65 and shifted the IL\u201017A\/IL\u201010 axis towards a Treg\u2010dominant profile. KYNA also enhanced fibroblast migration\n                      <jats:italic>in vitro<\/jats:italic>\n                      , suggesting a potential role in promoting wound healing under physiological conditions.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion and Implications<\/jats:title>\n                    <jats:p>\n                      KYNA exerts antifibrotic effects both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and in an\n                      <jats:italic>in vivo<\/jats:italic>\n                      model of renal fibrosis. The mechanisms involve multifaceted modulation of key signalling pathways related to fibrosis and immune response, highlighting KYNA as a promising therapeutic candidate for kidney fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.70469","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T04:16:28Z","timestamp":1777608988000},"page":"4448-4470","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kynurenic acid as a promising therapeutic agent in renal fibrosis: dual modulation of fibrosis and immune crosstalk"],"prefix":"10.1111","volume":"183","author":[{"given":"Sona","family":"Sykorova","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Comenius University Bratislava  Bratislava Slovak 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