Cellular signalling · 2026
CDK1 alleviates intrauterine adhesion progression by enhancing glycolysis and mitophagy in endometrial stem cells.
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Long Xicui, Yang Lijuan, Zhou Jianghong, Wang Sujie, Wu Mingjie, Han Xuesong
Аннотация
BACKGROUND AND OBJECTIVE: Intrauterine adhesion (IUA) often leading to recurrent miscarriage or infertility. The glycolytic activity and mitophagy level of endometrial stem cells (EnSCs) are crucial for endometrial regeneration. Although cyclin-dependent kinase 1 (CDK1) regulates both processes, its role in IUA is unknown. This study aimed to elucidate how CDK1 modulates EnSCs glycolysis and mitophagy during IUA progression.
METHODS: Experiments were performed using a lipopolysaccharide (LPS)-stimulated cellular injury model in vitro, as well as an IUA rat model in vivo. Uterine pathological damage and collagen deposition were assessed by HE and Masson staining. Mitochondrial membrane potential and autophagosome formation were examined using flow cytometry and transmission electron microscopy. Immunofluorescence, ELISA, Western blotting, CCK-8 assays, and various biochemical kits were used to detect relevant proteins, inflammatory cytokines, and glycolytic activity.
RESULTS: A reduced number of EnSCs was observed in IUA tissues, accompanied by impaired glycolysis and defective mitophagy. LPS stimulation markedly decreased EnSCs viability and proliferation, suppressed the stemness-related genes Oct4, Nanog, and Sox2, upregulated pro-apoptotic proteins Bax and cleaved caspase-3 as well as the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and downregulated the anti-apoptotic protein Bcl-2. CDK1 was lowly expressed in IUA, whereas CDK1 overexpression alleviated uterine injury, fibrosis, and inflammation in IUA rats, reduced stem cell loss, restored EnSCs proliferation and stemness, enhanced glycolysis and mitophagy, and inhibited apoptosis and inflammation. The beneficial effects of CDK1 overexpression were attenuated by the dynamin-related protein 1 (DRP1) inhibitor mitochondrial division inhibitor 1 (Mdivi-1) or the autophagy inhibitor 3-methyladenine (3-MA).
CONCLUSION: CDK1 restores EnSCs function and alleviates IUA progression by promoting DRP1-mediated mitophagy and enhancing glycolysis.
METHODS: Experiments were performed using a lipopolysaccharide (LPS)-stimulated cellular injury model in vitro, as well as an IUA rat model in vivo. Uterine pathological damage and collagen deposition were assessed by HE and Masson staining. Mitochondrial membrane potential and autophagosome formation were examined using flow cytometry and transmission electron microscopy. Immunofluorescence, ELISA, Western blotting, CCK-8 assays, and various biochemical kits were used to detect relevant proteins, inflammatory cytokines, and glycolytic activity.
RESULTS: A reduced number of EnSCs was observed in IUA tissues, accompanied by impaired glycolysis and defective mitophagy. LPS stimulation markedly decreased EnSCs viability and proliferation, suppressed the stemness-related genes Oct4, Nanog, and Sox2, upregulated pro-apoptotic proteins Bax and cleaved caspase-3 as well as the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, and downregulated the anti-apoptotic protein Bcl-2. CDK1 was lowly expressed in IUA, whereas CDK1 overexpression alleviated uterine injury, fibrosis, and inflammation in IUA rats, reduced stem cell loss, restored EnSCs proliferation and stemness, enhanced glycolysis and mitophagy, and inhibited apoptosis and inflammation. The beneficial effects of CDK1 overexpression were attenuated by the dynamin-related protein 1 (DRP1) inhibitor mitochondrial division inhibitor 1 (Mdivi-1) or the autophagy inhibitor 3-methyladenine (3-MA).
CONCLUSION: CDK1 restores EnSCs function and alleviates IUA progression by promoting DRP1-mediated mitophagy and enhancing glycolysis.