{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T17:41:02Z","timestamp":1792172462758,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01\u2010HD067449"],"award-info":[{"award-number":["NIH R01\u2010HD067449"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Following muscle injury, fibro\u2010adipogenic progenitors (FAPs) are rapidly activated and undergo apoptosis at the resolution stage, which is required for proper muscle regeneration. When excessive FAPs remain, it contributes to fibrotic and fatty infiltration, impairing muscle recovery. Mechanisms controlling FAP apoptosis remain poorly defined. We hypothesized that AMP\u2010activated protein kinase (AMPK) in FAPs mediates their apoptosis during the muscle regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To test, AMPK\u03b11<jats:sup>fl\/fl<\/jats:sup> PDGFR\u03b1<jats:sup>Cre<\/jats:sup> mice were used to knock out AMPK\u03b11 in FAPs. Following AMPK\u03b11 knockout, the mice were injected with phosphate\u2010buffered saline or glycerol to induce muscle injury. Tibialis anterior muscle and FAPs were collected at 3, 7 and 14\u00a0days post\u2010injury (dpi) for further analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that AMPK\u03b11 deletion in FAPs enhanced p65 translocation to the nuclei by 110% (<jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). AMPK\u03b11 knockout group had a higher gene expression of MMP\u20109 (matrix metalloproteinase\u20109) by 470% (<jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and protein level by 39% (<jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Loss of AMPK\u03b11 up\u2010regulated the active TGF\u2010\u03b21 (transforming growth factor\u2010\u03b21) levels by 21% (<jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). TGF\u2010\u03b2 promoted apoptotic resistance, because AMPK\u03b11\u2010deficient group had 36% lower cleaved Caspase 3 (cCAS3) content (<jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Fibrotic differentiation of FAPs was promoted, with increased collagen protein level by 54% (<jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Moreover, obesity decreased phosphorylation of AMPK by 54% (<jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05), which decreased cCAS3 in FAPs by 44% (<jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and elevated collagen accumulation (52%; <jats:italic>n<\/jats:italic>\u00a0=\u00a03; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) during muscle regeneration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These data suggest that AMPK is a key mediator of FAPs apoptosis, and its inhibition due to obesity results in fibrosis of regenerated muscle.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13150","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T01:51:40Z","timestamp":1670982700000},"page":"479-492","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["AMP\u2010activated protein kinase inhibition in fibro\u2010adipogenic progenitors impairs muscle regeneration and increases fibrosis"],"prefix":"10.1002","volume":"14","author":[{"given":"Xiangdong","family":"Liu","sequence":"first","affiliation":[{"name":"Laboratory of Nutrigenomics and Growth Biology, Department of Animal Sciences Washington State University  Pullman Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Laboratory of Nutrigenomics and Growth Biology, Department of Animal Sciences Washington State University  Pullman Washington USA"},{"name":"College of 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