{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:24:07Z","timestamp":1783607047880,"version":"3.55.0"},"reference-count":41,"publisher":"American Society for Clinical Investigation","issue":"3","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["1I01BX005792"],"award-info":[{"award-number":["1I01BX005792"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"crossref","award":["2I01BX002006"],"award-info":[{"award-number":["2I01BX002006"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"crossref"}]},{"name":"American Society of Nephrology Carl W. Gottschalk Research Scholar Grant","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,9]]},"abstract":"<jats:p>\n                    Mechanisms responsible for skeletal muscle kidney crosstalk have not been defined. We have determined that a circulating mediator, signal regulatory protein \u03b1 (SIRP\u03b1), impairs intracellular insulin-mediated functions. To elucidate the effect of myokine SIRP\u03b1 on diabetic kidney disease (DKD), flox mice and muscle-specific (m-specific) SIRP\u03b1-KO mice were subjected to an obesity-induced model of diabetes, high-fat diet (HFD; 60%) or insulin-deficient hyperglycemia model, streptozotocin (STZ), and were subsequently exposed to anti-SIRP\u03b1 monoclonal antibodies. In the obesity-induced diabetic mice, serum SIRP\u03b1 increased. Genetic deletion of muscle SIRP\u03b1 protected against obesity and improved intracellular insulin signaling in muscle and adipose tissue, with reduced intramuscular fat deposition when compared with\n                    <jats:italic>flox<\/jats:italic>\n                    mice on HFD. Moreover,\n                    <jats:italic>mSIRP<\/jats:italic>\n                    \u03b1-KO mice displayed enhanced kidney tubular fatty acid oxidation (FAO) expression with suppressed intraorgan triglycerides deposition, and importantly, protection against DKD. Conversely, exogenous SIRP\u03b1 impaired kidney proximal tubular cell FAO, ATP production, and exacerbated fibrosis. Finally, suppressing SIRP\u03b1 in skeletal muscles or treatment with anti-SIRP\u03b1 monoclonal antibodies in STZ-treated mice mitigated cachexia, hyperlipidemia, kidney triglyceride deposition, and renal dysfunction in spite of significant hyperglycemia. Importantly, serum SIRP\u03b1 was upregulated in patients with DKD. In conclusion, SIRP\u03b1 serves as a potential biomarker and therapeutic target in DKD.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.183392","type":"journal-article","created":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T19:00:48Z","timestamp":1770577248000},"source":"Crossref","is-referenced-by-count":1,"title":["Myokine SIRP\u03b1 exacerbates kidney disease in diabetes"],"prefix":"10.1172","volume":"11","author":[{"given":"Jiao","family":"Wu","sequence":"first","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine (BCM), Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Russo","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Universit\u00e0 degli Studi di Genova, Genoa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Verzola","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Universit\u00e0 degli Studi di Genova, Genoa, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingtian","family":"Li","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine (BCM), Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena","family":"Zhang","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine (BCM), Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhuvaneswari","family":"Krishnan","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology, BCM, Houston, Texas, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Sheikh-Hamad","sequence":"additional","affiliation":[{"name":"Nephrology Division, Department of Medicine, Baylor College of Medicine (BCM), Houston, Texas, USA."},{"name":"Nephrology Division, Department of Medicine, Michael E. 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