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Human umbilical cord mesenchymal stem cell-derived exosomal miR-455-3p targets CAMK2N1 to improve trophoblast cell injury in gestational diabetes mellitus

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机构： [1]Department of Medical Genetics, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, 650000, China. [2]Department of Obstetrics, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China. [3]National Health Commission Key Laboratory of Preconception Health Birth in Western China, Kunming, Yunan, China. [4]Department of Medical Genetics, Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, Kunming, Yunan, China.

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关键词： Human umbilical cord mesenchymal stem cell Exosome MicroRNA-455-3p Calcium/calmodulindependent protein kinase 2 inhibitor 1 Trophoblast cell Gestational diabetes mellitus

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We aimed to probe the effect of microRNA (miR)-455-3p derived from human umbilical cord mesenchymal stem cell exosomes (hucMSCs-Exos) in targeting calcium/calmodulin-dependent protein kinase 2 inhibitor 1 (CAMK2N1) to mitigate trophoblast cell injury in gestational diabetes mellitus (GDM).hucMSCs were cultured, and Exos were isolated and characterized using transmission electron microscopy and Western blot (WB) for exosomal surface markers CD63, TSG101, and Calnexin. An in vitro GDM model was established by exposing human trophoblast cells (HRT-8/SVneo) to high glucose (HG), followed by intervention with Exos or overexpression of CAMK2N1. RT-qPCR or WB was applied to test miR-455-3p and CAMK2N1 expression levels. CCK-8 assay was adopted to assess cell proliferation, Transwell assay was applied to test cell migration, and flow cytometry was implemented to assess cell apoptosis. Bioinformatics websites and a dual-luciferase reporter gene assay were conducted to verify the targeting relationship between miR-455-3p and CAMK2N1.The successfully isolated Exos expressed the exosomal markers CD63 and TSG101. Treatment with hucMSCs-Exos and hucMSCs-Exos carrying miR-455-3p mimic enhanced the migration and proliferation of HG-induced HRT-8/SVneo cells while reducing cell apoptosis. In contrast, the miR-455-3p inhibitor and overexpression of CAMK2N1 reversed these protective effects, leading to decreased cell migration and proliferation and increased apoptosis. Furthermore, bioinformatics analysis and experimental validation confirmed that miR-455-3p directly targeted and negatively regulated CAMK2N1.miR-455-3p derived from hucMSCs-Exos exerts a protective effect against trophoblast cell injury in GDM by targeting and downregulating CAMK2N1.© 2025. The Author(s).

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大类 | 3 区医学

小类 | 3 区内分泌学与代谢

第一作者：

第一作者机构： [1]Department of Medical Genetics, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, 650000, China. [3]National Health Commission Key Laboratory of Preconception Health Birth in Western China, Kunming, Yunan, China. [4]Department of Medical Genetics, Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, Kunming, Yunan, China.

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通讯机构： [1]Department of Medical Genetics, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, No. 157 Jinbi Road, Xishan District, Kunming, Yunnan, 650000, China. [3]National Health Commission Key Laboratory of Preconception Health Birth in Western China, Kunming, Yunan, China. [4]Department of Medical Genetics, Yunnan Provincial Key Laboratory of Birth Defects and Genetic Diseases, NHC Key Laboratory of Healthy Birth and Birth Defect Prevention in Western China, Kunming, Yunan, China.

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Human umbilical cord mesenchymal stem cell-derived exosomal miR-455-3p targets CAMK2N1 to improve trophoblast cell injury in gestational diabetes mellitus

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