{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T19:23:44Z","timestamp":1771615424695,"version":"3.50.1"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T00:00:00Z","timestamp":1771545600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Type 2 cardiorenal syndrome (CRS), driven by chronic myocardial infarction (MI), is characterized by renal fibrosis and oxidative stress, yet underlying mechanisms and therapies are poorly defined. This study investigated whether resistance training protects against MI-induced renal injury via the FNDC5\/Irisin axis. Male wild-type (WT) and global Fndc5 knockout (KO) mice were subjected to MI or sham surgery and then allocated to sedentary or ladder-climbing resistance training groups for 4 weeks (n\u2009=\u20098 per group). An in vitro model was established using H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -stimulated human renal tubular (HKC) cells. We found that resistance training upregulated renal FNDC5 expression, lowered serum creatinine and blood urea nitrogen levels, and attenuated tubular injury in WT mice with CRS, but these benefits were markedly blunted in KO mice. Training reduced renal malondialdehyde content, enhanced superoxide dismutase 1\/2 expression, and decreased collagen deposition alongside downregulation of fibrotic markers (Collagen-I\/III, \u03b1-SMA). These improvements were associated with suppressed activation of the renal TGF-\u03b21\/Smad2\/3 pathway in WT but not in KO mice. In HKC cells, recombinant Irisin and the AMPK agonist AICAR mitigated H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    -induced oxidative stress, fibrotic protein expression, and Smad2\/3 phosphorylation. We conclude that resistance exercise ameliorates renal oxidative stress and fibrosis in Type 2 CRS, effects that are substantially mediated by, but not exclusively dependent on, the FNDC5\/Irisin axis. Our work highlights FNDC5\/Irisin as a key amplifier of exercise-induced renoprotection and supports the therapeutic potential of resistance training in cardiorenal syndrome.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0342468","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:38:30Z","timestamp":1771612710000},"page":"e0342468","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["FNDC5\/Irisin-dependent renoprotection of resistance training in myocardial infarction\u2013induced Type 2 cardiorenal syndrome"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2690-6903","authenticated-orcid":true,"given":"Weiyu","family":"Fu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenqian","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7907-5407","authenticated-orcid":true,"given":"Kai","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2026,2,20]]},"reference":[{"key":"pone.0342468.ref001","doi-asserted-by":"crossref","first-page":"53","DOI":"10.3389\/fphys.2018.00053","article-title":"Pyridostigmine improves the effects of resistance exercise training after myocardial infarction in rats","volume":"9","author":"DJ Feriani","year":"2018","journal-title":"Front Physiol"},{"issue":"1","key":"pone.0342468.ref002","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1002\/ehf2.13730","article-title":"Urinary liver-type fatty acid-binding protein as a prognostic marker in patients with acute heart failure","volume":"9","author":"T Sunayama","year":"2022","journal-title":"ESC Heart Fail"},{"issue":"3","key":"pone.0342468.ref003","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1002\/ejhf.16","article-title":"Long-term prognostic impact of therapeutic strategies in patients with idiopathic dilated cardiomyopathy: changing mortality over the last 30 years","volume":"16","author":"M Merlo","year":"2014","journal-title":"Eur J Heart Fail"},{"key":"pone.0342468.ref004","doi-asserted-by":"crossref","first-page":"852095","DOI":"10.3389\/fonc.2022.852095","article-title":"FNDC5 causes resistance to sorafenib by activating the PI3K\/Akt\/Nrf2 pathway in hepatocellular carcinoma cells","volume":"12","author":"H Liu","year":"2022","journal-title":"Front Oncol"},{"issue":"5","key":"pone.0342468.ref005","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1177\/2047487320913379","article-title":"Secondary prevention through comprehensive cardiovascular rehabilitation: From knowledge to implementation. 2020 update. 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