{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T21:36:20Z","timestamp":1793223380964,"version":"4.5.0"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A2C2002720"],"award-info":[{"award-number":["2019R1A2C2002720"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C2009367"],"award-info":[{"award-number":["2022R1A2C2009367"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2022R1A2C1002956"],"award-info":[{"award-number":["2022R1A2C1002956"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS\u20102025\u201000520874"],"award-info":[{"award-number":["RS\u20102025\u201000520874"]}],"id":[{"id":"10.13039\/501100003725","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":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Muscle atrophy is commonly associated with kidney dysfunction in patients with renal disease. However, the effects of skeletal muscle loss per se on kidney function have not been fully elucidated. Here, we examined muscle\u2013kidney crosstalk by evaluating the role of muscle\u2010derived small extracellular vesicles (EVs) on the progression of kidney injury.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A denervation\u2010induced muscle loss model was established, and kidney inflammation and fibrosis were evaluated in unilateral ureteral obstruction (UUO)\u2010induced kidney injury and adenine diet\u2010induced chronic kidney disease models. Changes in small EV markers (CD9, CD63, CD81 and Alix) were measured. GW4869, an inhibitor of EV biogenesis and release, was used to confirm the role of denervated muscle\u2010derived small EVs on the progression of kidney fibrosis. To obtain direct evidence on the crosstalk, EVs were isolated from plasma of denervated mice and conditioned media from differentiated myotubes and treated in\u00a0vivo and in\u00a0vitro. To determine the effect of exercise\u2010induced EVs on kidney fibrosis, EVs isolated from exercised mice and trained humans were treated to TGF\u03b21\u2010stimulated mProx24 renal tubular epithelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Denervation aggravated kidney injury, as shown by a 10% increase in albuminuria and upregulation of inflammatory and fibrotic markers in the kidney. Significant interactions between denervation and UUO were observed for renal \u03b1SMA (\n                      <jats:italic>F<\/jats:italic>\n                      \u2009=\u200947.19,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and FN (\n                      <jats:italic>F<\/jats:italic>\n                      \u2009=\u200919.06,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0001) expression. EV production and secretion were markedly increased in damaged muscle, both in\u00a0vivo and in\u00a0vitro. Pharmacological depletion of EVs using GW4869 via intraperitoneal and intramuscular injection reduced kidney injury by over 20%. Furthermore, injection of EVs from denervated muscle into UUO mice, as well as treatment of mProx24 cells with EVs from either denervated mice or damaged C2C12 myotubes, significantly amplified renal injury. Among the EV cargo, miR\u201021a\u20103p\u2014identified as a regulator of Ppargc1a\u2014was elevated over 10\u2010fold in EVs from denervated muscle compared with sham controls. Importantly, EV\u2010induced injury in mProx24 cells was reversed by pretreatment with a miR\u201021a inhibitor. In contrast, exercise downregulated miR\u201021a\u20103p expression in muscle, and EVs derived from exercised mice and humans attenuated kidney fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings provide novel evidence that skeletal muscle loss can serve as an upstream contributor to kidney disease. Muscle\u2010derived EVs from damaged tissue exacerbate, while those from exercised muscle ameliorate, kidney injury, partly through miR\u201021a\u20103p regulation. These results highlight the critical role of miRNAs within muscle\u2010derived EVs in maintaining kidney homeostasis and suggest their potential as therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13861","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T05:44:46Z","timestamp":1749793486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Small Extracellular Vesicles Derived From Damaged Muscle Aggravate Kidney Injury Progression"],"prefix":"10.1002","volume":"16","author":[{"given":"Songling","family":"Jiang","sequence":"first","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, College of Pharmacy Ewha Womans University  Seoul Republic of Korea"},{"name":"Integrated Omics Institute Wonkwang University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seunghee","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science and Food Management Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oran","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Nutritional Science and Food Management Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wonhyo","family":"Seo","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, College of Pharmacy Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eun\u2010Jung","family":"Jin","sequence":"additional","affiliation":[{"name":"Integrated Omics Institute Wonkwang University  Iksan Republic of Korea"},{"name":"Department of Biomedical Materials Science, Graduate School of JABA Wonkwang University  Iksan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hunjoo","family":"Ha","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, College of Pharmacy Ewha Womans University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2936-863X","authenticated-orcid":false,"given":"Joo\u00a0Young","family":"Huh","sequence":"additional","affiliation":[{"name":"College of Pharmacy Chung\u2010Ang University  Seoul Republic of Korea"},{"name":"Department of Global Innovative Drugs The Graduate School of Chung\u2010Ang University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-021-00498-0"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.10261013"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00411.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2018.08.014"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.23876\/j.krcp.21.175"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gheart.2012.05.003"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.697204"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnaa016"},{"issue":"6478","key":"e_1_2_8_10_1","article-title":"The Biology, Function, and Biomedical Applications of Exosomes","volume":"367","author":"Kalluri R.","year":"2020","journal-title":"Science (1979)"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2016112117"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12945"},{"key":"e_1_2_8_13_1","article-title":"Tibial Nerve Transection \u2010 A Standardized Model for Denervation\u2010Induced Skeletal Muscle Atrophy in Mice","volume":"81","author":"Batt J. 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