{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:14:27Z","timestamp":1789535667236,"version":"build-2803163510"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"stoneygate"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) affects approximately 14% of the UK population and is associated with significant exercise intolerance, partly due to skeletal muscle dysfunction. While exercise is a potential therapeutic strategy, the molecular response of skeletal muscle to exercise in CKD remains poorly understood. This study aimed to characterise transcriptomic changes in skeletal muscle 24 hours after aerobic (AE) or combined aerobic and resistance exercise (CE) in non-dialysis CKD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study utilised muscle biopsies from participants in the ExTRA CKD trial with stage 3b\u20134 CKD stages 3b-4 (AE: 24 (15\u201332) ml\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      ; CE: 25 (19\u201331) ml\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      ). Participants (n\u2009=\u20094 per group) were randomised to 12 weeks of thrice-weekly AE or CE. Vastus lateralis skeletal muscle biopsies were collected at baseline and 24h after the first bout of exercise. RNA was extracted for Bulk RNA sequencing. Bulk RNA sequencing was performed, and differentially expressed genes (DEGs) were identified between baseline and post-exercise samples, followed by pathway enrichment analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following AE, 1480 genes were upregulated and 1554 downregulated. CE resulted in 556 upregulated and 115 downregulated genes. The most upregulated gene after AE was\n                      <jats:italic>CHI3L1<\/jats:italic>\n                      (log\u2082FC 10.7), followed by\n                      <jats:italic>SAA2<\/jats:italic>\n                      and\n                      <jats:italic>PTX3<\/jats:italic>\n                      , all associated with inflammation. After CE,\n                      <jats:italic>SFN<\/jats:italic>\n                      (log\u2082FC 6.8) and\n                      <jats:italic>MT1A<\/jats:italic>\n                      were among the most highly upregulated. Enrichment analysis showed strong activation of inflammatory and cellular senescence pathways, and downregulation of mitochondrial function-related processes, particularly after AE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both AE and CE triggered robust inflammatory gene expression responses in CKD skeletal muscle, which may be indicative of early repair processes. Unexpectedly, mitochondrial-related pathways were downregulated at 24h post exercise. In the absence of earlier post exercise timepoints, it is not possible to determine whether these findings reflect impaired mitochondrial adaptation, or instead represent a recovery phase return of mitochondrial gene expression levels to baseline. These results highlight mitochondrial dysfunction may be a potential barrier to effective exercise adaptation and a possible therapeutic target in this population.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0324303","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T18:41:18Z","timestamp":1772044878000},"page":"e0324303","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Transcriptomic response of skeletal muscle to acute aerobic versus combined exercise in chronic kidney disease"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2111-3832","authenticated-orcid":true,"given":"Luke A.","family":"Baker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Graham-Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Wilkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3869-8972","authenticated-orcid":true,"given":"Emma L.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"pone.0324303.ref001","unstructured":"UK KR. 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