{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:09:46Z","timestamp":1792613386302,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873613"],"award-info":[{"award-number":["81873613"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82000727"],"award-info":[{"award-number":["82000727"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["5R01DK037175"],"award-info":[{"award-number":["5R01DK037175"]}],"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":[[2026,4]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n High glucose induces mitochondrial dysfunction in podocytes, contributing to the development of diabetic nephropathy (DN). There is increasing evidence that muscles play a protective role by secreting myokines into the kidneys. Here, we investigated how skeletal muscle influences podocyte health via muscle\u2013kidney crosstalk.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n To increase myokine release, we overexpressed PGC\u20101\u03b1 specifically in skeletal muscle (mPGC\u20101\u03b1) and crossed these mice with db\/m mice to generate diabetic mPGC\u20101\u03b1:db\/db mice. In parallel, db\/db mice were treated intraperitoneally with recombinant murine interleukin\u201015 (IL\u201015). Mechanistic studies were performed using isolated primary podocytes and cultured podocyte cell lines.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Compared with db\/db controls, mPGC\u20101\u03b1:db\/db mice exhibited reduced urinary albumin excretion (\n p<\/jats:italic>\n \u2009<\u20090.001), mesangial matrix expansion (\n p<\/jats:italic>\n \u2009<\u20090.001), glomerular basement membrane thickening (\n p<\/jats:italic>\n \u2009<\u20090.001) and urinary podocin excretion (\n p<\/jats:italic>\n \u2009<\u20090.001), along with increased podocyte number (\n p<\/jats:italic>\n \u2009<\u20090.001). Podocytes from mPGC\u20101\u03b1:db\/db mice showed higher expression of Nephrin and COX IV (\n p<\/jats:italic>\n \u2009<\u20090.05) and upregulation of multiple mitochondrial function\u2010related genes, notably OPA1 (\n p<\/jats:italic>\n \u2009<\u20090.05). Skeletal muscle from mPGC\u20101\u03b1:db\/db mice displayed elevated IL\u201015 mRNA (\n p<\/jats:italic>\n \u2009<\u20090.05) and protein (\n p<\/jats:italic>\n \u2009<\u20090.01) levels, accompanied by increased plasma IL\u201015 concentrations (\n p<\/jats:italic>\n \u2009<\u20090.05). IL\u201015 treatment enhanced podocyte mitochondrial respiration, including basal oxygen consumption rate (OCR,\n p<\/jats:italic>\n \u2009<\u20090.05), ATP\u2010coupled respiration (\n p<\/jats:italic>\n \u2009<\u20090.05) and maximal respiration (\n p<\/jats:italic>\n \u2009<\u20090.05). IL\u201015 preserved mitochondrial fusion under high\u2010glucose conditions by increasing OPA1 expression (\n p<\/jats:italic>\n \u2009<\u20090.05) and promoted OPA1 transcription via histone H3 acetylation at its promoter (\n p<\/jats:italic>\n \u2009<\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Skeletal muscle\u2010derived IL\u201015 mediates renal protection by maintaining mitochondrial fusion in podocytes during DN progression. Targeting this pathway may offer a therapeutic strategy to preserve kidney function and slow progression to end\u2010stage renal disease.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70256","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T06:53:47Z","timestamp":1773816827000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["IL\u201015 Links Muscle\u2013Kidney Crosstalk to Preserving Podocyte Mitochondrial Fusion and Attenuating Diabetic Nephropathy"],"prefix":"10.1002","volume":"17","author":[{"given":"Yin","family":"Li","sequence":"first","affiliation":[{"name":"Nephrology Division The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialing","family":"Rao","sequence":"additional","affiliation":[{"name":"Nephrology Division The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyan","family":"Lai","sequence":"additional","affiliation":[{"name":"Nephrology Division The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Sun","sequence":"additional","affiliation":[{"name":"Nephrology Division The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongchun","family":"Lin","sequence":"additional","affiliation":[{"name":"Nephrology Division The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nephrology Division The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengchun","family":"Ye","sequence":"additional","affiliation":[{"name":"Nephrology Division The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyong","family":"Hu","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine Baylor College of Medicine Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0220-3616","authenticated-orcid":false,"given":"Hui","family":"Peng","sequence":"additional","affiliation":[{"name":"Nephrology Division The Third Affiliated Hospital of Sun Yat\u2010sen University Guangzhou 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