{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:35:24Z","timestamp":1790775324884,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30NS055077"],"award-info":[{"award-number":["P30NS055077"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000738","name":"U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01\u2010BX001456"],"award-info":[{"award-number":["I01\u2010BX001456"]}],"id":[{"id":"10.13039\/100000738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["17IBDG33780000"],"award-info":[{"award-number":["17IBDG33780000"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["UL1TR000454"],"award-info":[{"award-number":["UL1TR000454"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 DK095610"],"award-info":[{"award-number":["R01 DK095610"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR060268"],"award-info":[{"award-number":["R01 AR060268"]}],"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":[[2018,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The treatment of muscle wasting is accompanied by benefits in other organs, possibly resulting from muscle\u2013organ crosstalk. However, how the muscle communicates with these organs is less understood. Two microRNAs (miRs), miR\u201023a and miR\u201027a, are located together in a gene cluster and regulate proteins that are involved in the atrophy process. MiR\u201023a\/27a has been shown to reduce muscle wasting and act as an anti\u2010fibrotic agent. We hypothesized that intramuscular injection of miR\u201023a\/27a would counteract both muscle wasting and renal fibrosis lesions in a streptozotocin\u2010induced diabetic model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We generated an adeno\u2010associated virus (AAV) that overexpresses the miR\u201023a\u223c27a\u223c24\u20102 precursor RNA and injected it into the tibialis anterior muscle of streptozotocin\u2010induced diabetic mice. Muscle cross\u2010section area (immunohistology plus software measurement) and muscle function (grip strength) were used to evaluate muscle atrophy. Fibrosis\u2010related proteins were measured by western blot to monitor renal damage. In some cases, AAV\u2010GFP was used to mimic the miR movement\n                      <jats:italic>in vivo<\/jats:italic>\n                      , allowing us to track organ redistribution by using the Xtreme Imaging System.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The injection of AAV\u2010miR\u201023a\/27a increased the levels of miR\u201023a and miR\u201027a as well as increased phosphorylated Akt, attenuated the levels of FoxO1 and PTEN proteins, and reduced the abundance of TRIM63\/MuRF1 and FBXO32\/atrogin\u20101 in skeletal muscles. It also decreased myostatin mRNA and protein levels as well as the levels of phosphorylated pSMAD2\/3. Provision of miR\u201023a\/27a attenuates the diabetes\u2010induced reduction of muscle cross\u2010sectional area and muscle function. Curiously, the serum BUN of diabetic animals was reduced in mice undergoing the miR\u201023a\/27a intervention. Renal fibrosis, evaluated by Masson trichromatic staining, was also decreased as were kidney levels of phosphorylated SMAD2\/3, alpha smooth muscle actin, fibronectin, and collagen. In diabetic mice injected intramuscularly with AAV\u2010GFP, GFP fluorescence levels in the kidneys showed linear correlation with the levels in injected muscle when examined by linear regression. Following intramuscular injection of AAV\u2010miR\u201023a\u223c27a\u223c24\u20102, the levels of miR\u201023a and miR\u201027a in serum exosomes and kidney were significantly increased compared with samples from control virus\u2010injected mice; however, no viral DNA was detected in the kidney.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We conclude that overexpression of miR\u201023a\/27a in muscle prevents diabetes\u2010induced muscle cachexia and attenuates renal fibrosis lesions via muscle\u2013kidney crosstalk. Further, this crosstalk involves movement of miR potentially through muscle originated exosomes and serum distribution without movement of AAV. These results could provide new approaches for developing therapeutic strategies for diabetic nephropathy with muscle wasting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.12296","type":"journal-article","created":{"date-parts":[[2018,3,27]],"date-time":"2018-03-27T02:22:45Z","timestamp":1522117365000},"page":"755-770","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":143,"title":["miRNA\u201023a\/27a attenuates muscle atrophy and renal fibrosis through muscle\u2010kidney crosstalk"],"prefix":"10.1002","volume":"9","author":[{"given":"Aiqing","family":"Zhang","sequence":"first","affiliation":[{"name":"Renal Division, Dept. of Medicine Emory University  Atlanta GA USA"},{"name":"Department of Pediatric Nephrology The Second Affiliated Hospital of Nanjing Medical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Li","sequence":"additional","affiliation":[{"name":"Renal Division, Dept. of Medicine Emory University  Atlanta GA USA"},{"name":"Molecular Biology Laboratory, Guanganmen Hospital Chinese Academy of traditional Chinese Medicine  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division, Dept. of Medicine Emory University  Atlanta GA USA"},{"name":"Institute of Nephrology, Zhong Da Hospital Southeast University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet D.","family":"Klein","sequence":"additional","affiliation":[{"name":"Renal Division, Dept. of Medicine Emory University  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Russ","family":"Price","sequence":"additional","affiliation":[{"name":"Renal Division, Dept. of Medicine Emory University  Atlanta GA USA"},{"name":"Research Service Line Atlanta Veterans Affairs Medical Center  Decatur IL USA"},{"name":"Department of Biochemistry and Molecular Biology, Brody School of Medicine East Carolina University  Greenville NC USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1023-8499","authenticated-orcid":false,"given":"Xiaonan H.","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division, Dept. of Medicine Emory University  Atlanta GA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,3,26]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"238","article-title":"Malnutrition in uremia","volume":"14","author":"Avram MM","year":"1994","journal-title":"Semin 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