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作者

Haijiao Wang, Baochang Shi, Wenting Song, Lu Lu, Akhilesh K Bajpai, Qiu Li

作者单位

Affiliations ¹ Department of Endocrinology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China. ² Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong, China. ³ Department of Endocrinology, Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. ⁴ Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN, USA. ⁵ Shandong Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Institute of Endocrine and Metabolic Diseases, Jinan, Shandong, China. ⁶ Department of Endocrinology, Shandong Institute of Endocrine and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. ⁷ "Chuangxin China" Innovation Base of Stem Cell and Gene Therapy for Endocrine Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. ⁸ Shandong Engineering Laboratory of Prevention and Control for Endocrine and Metabolic Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. ⁹ 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.

刊名

Biomarker insights

年份

2026

卷号

Vol.21

ISSN

1177-2719

关键词

exosome hypoxia miRNA sequencing normoxia skeletal muscle.

摘要

Background: Hypoxia alters skeletal muscle metabolism and function through complex regulatory mechanisms, including exosome-mediated microRNA signaling. Objectives: This study profiled exosomal miRNAs from hypoxic human skeletal muscle cells to explore their roles in hypoxic adaptation. Design: Human skeletal muscle cells were cultured under normoxic or hypoxic conditions, and secreted exosomes were isolated for comprehensive molecular profiling. High-throughput miRNA sequencing combined with ...更多

Background: Hypoxia alters skeletal muscle metabolism and function through complex regulatory mechanisms, including exosome-mediated microRNA signaling. Objectives: This study profiled exosomal miRNAs from hypoxic human skeletal muscle cells to explore their roles in hypoxic adaptation. Design: Human skeletal muscle cells were cultured under normoxic or hypoxic conditions, and secreted exosomes were isolated for comprehensive molecular profiling. 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. Methods: HSMCs were cultured under normoxic or hypoxic conditions for 24 hours. Exosomes were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and immunoblotting. Exosomal miRNAs were profiled using high-throughput sequencing, followed by differential expression, target prediction, enrichment, and network analyses. Results: Isolated exosomes displayed typical morphology and expressed markers CD9, CD63, and TSG101. Seventy-four miRNAs were significantly dysregulated under hypoxia , including upregulated hsa-miR-210-3p and downregulated hsa-miR-486-5p, hsa-miR-127-3p, and hsa-miR-126-3p. Predicted targets 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 , 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. Conclusions: 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.收起

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