Bone Marrow Mesenchymal Stromal Cells and Their Derived Extracellular Vesicles Protect Pancreatic Beta‐TC‐6 Cells From Hypoxia‐Induced Injury via miR‐539‐3p‐Mediated Downregulation of CD36 Expression
Na Lin, Yaoyao Liang, Minying Tang, Fei Liu, Liuyan Chen, Lvying Wu, Yunfeng Fu, Zhuoyu Li, Lingfeng Zhu, Jin Chen
TL;DR
Bone marrow cells and their vesicles protect pancreatic cells from hypoxia by reducing CD36 expression through miR-539-3p, offering potential for diabetes therapy.
Contribution
Identifies miR-539-3p as a novel mediator of BMSC and BMSC-EV protection against hypoxia in pancreatic beta cells via CD36 downregulation.
Findings
BMSCs and BMSC-EVs enhance hypoxic beta-TC-6 cell viability and survival.
miR-539-3p suppresses CD36 expression by targeting its 3'UTR, reducing hypoxia-induced injury.
CD36 knockdown restores protective effects abrogated by miR-539-3p inhibition.
Abstract
Bone marrow mesenchymal stromal cells (BMSCs) have been shown to enhance the function of pancreatic beta‐cells under hypoxic conditions. However, the precise mechanisms underlying this protective effect remain elusive. In this study, we established a hypoxic beta‐cell model using murine pancreatic beta‐TC‐6 cells to investigate the protective effect and mechanism of BMSCs and their secreted extracellular vesicles (BMSC‐EVs) on hypoxic β cells. Our findings reveal that coculture with BMSCs or BMSC‐EVs significantly enhances the viability and survival of hypoxic beta‐TC‐6 cells. Molecularly, hypoxic conditions trigger an upregulation of CD36 in beta‐TC‐6 cells, a response that is counteracted by BMSCs or BMSC‐EVs. Through a screening process for microRNAs (miRNAs) capable of degrading CD36 mRNA, we identified miR‐539‐3p as a potent suppressor of CD36 expression. The miR‐539‐3p mimic was…
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Taxonomy
TopicsExtracellular vesicles in disease · Mesenchymal stem cell research · Pregnancy and preeclampsia studies