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High-throughput miRNA sequencing combined with integrative bioinformatic analyses was used to uncover hypoxia-responsive regulatory networks and key miRNA hubs involved in skeletal muscle adaptation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>HSMCs were cultured under normoxic or hypoxic conditions for 24\u2009hours. Exosomes were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and immunoblotting. Exosomal miRNAs (n\u2009=\u20093 per group) were profiled using high-throughput sequencing, followed by differential expression, target prediction, enrichment, and network analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Isolated exosomes displayed typical morphology (mean size: 82.4\u2009\u00b1\u20093.2\u2009nm) and expressed markers CD9, CD63, and TSG101. Seventy-four miRNAs were significantly dysregulated under hypoxia (23 upregulated, 51 downregulated; FDR\u2009&lt;\u20090.05, |log2FC|\u2009\u2a7e\u20091), including upregulated hsa-miR-210-3p and downregulated hsa-miR-486-5p, hsa-miR-127-3p, and hsa-miR-126-3p. Predicted targets (~2000 genes) included 451 genes differentially expressed in hypoxic versus normoxic skeletal muscle cells. Functional enrichment highlighted cancer-related, MAPK, PI3K-Akt, and HIF-1 signaling pathways, along with muscle differentiation processes. Network analysis identified hsa-miR-20a-5p as a central regulatory hub (46 targets), followed by hsa-miR-24-3p and hsa-miR-152-3p. hsa-miR-24-3p showed the strongest disease associations in the miRNA-disease network.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Hypoxia induces distinct exosomal miRNA signatures in skeletal muscle, regulating genes involved in differentiation, migration, and stress response. These findings suggest that exosome-mediated miRNA signaling contributes to hypoxia-driven muscle adaptation and intercellular communication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/11772719261427170","type":"journal-article","created":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T13:01:22Z","timestamp":1772283682000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular Insights into the Regulatory Mechanisms Mediated by Hypoxia-Conditioned Skeletal Muscle Exosomal miRNAs"],"prefix":"10.1177","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-6055-2370","authenticated-orcid":false,"given":"Haijiao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6872-1491","authenticated-orcid":false,"given":"Baochang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenting","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrine Glucose &amp; Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akhilesh K.","family":"Bajpai","sequence":"additional","affiliation":[{"name":"Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Key Laboratory of Endocrine Glucose &amp; Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"},{"name":"Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China"},{"name":"Department of Endocrinology, Shandong Institute of Endocrine and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"},{"name":"\u201cChuangxin China\u201d Innovation Base of Stem Cell and Gene Therapy for Endocrine Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"},{"name":"Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"},{"name":"Shandong Engineering Research Center of Stem Cell and Gene Therapy for Endocrine and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/1568006043335989"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61249-0"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/life12071041"},{"issue":"10","key":"e_1_3_3_5_2","article-title":"Global burden of peripheral artery disease and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019","volume":"11","author":"Collaborators GBDPAD","year":"2023","unstructured":"Collaborators GBDPAD. 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