期刊
FASEB JOURNAL
卷 36, 期 11, 页码 -出版社
WILEY
DOI: 10.1096/fj.202201079RR
关键词
adipose-derived mesenchymal stem cells; diabetic wound; graphene oxide; Linc00324; miR-7977
资金
- National Natural Science Foundation of China [82072819]
- National Natural Science Foundation of Jiangsu Province [BK20201155]
- China Postdoctoral Science Foundation [2019T120462]
- Jiangsu Postdoctoral Science Foundation [2019K155]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX20_2456, KYCX20_2480]
Graphene oxide (GO) can inhibit the apoptosis of adipose-derived mesenchymal stem cells (Ad-MSCs) induced by high glucose and promote diabetic wound healing. The study found that GO regulates the expression of STK4 and downstream signaling pathways by interacting with Linc00324 and miR-7977.
Many studies have shown that graphene oxide (GO) promotes proliferation and differentiation of a variety of stem cells. However, its effect on adipose-derived mesenchymal stem cell (Ad-MSCs) apoptosis is still unclear. Apoptosis is a significant factor affecting stem cell-based treatment of diabetic wounds. Therefore, we explored the effect of GO on Ad-MSC apoptosis and diabetic wound healing. In this study, qRT-PCR was used to detect Ad-MSC expression of LncRNAs, miRNAs, and mRNAs under high-glucose environment. RNA immunoprecipitation (RIP), RNA pull-down, and luciferase assays were used to detect interactions of specific lncRNAs, miRNAs, and mRNAs. The effects of GO on Ad-MSC apoptosis were explored by flow cytometry, TUNEL assay, and Western blot. A diabetic wound model was used to explore the function of Linc00324 on Ad-MSC reparative properties in vivo. As a result, GO inhibited high glucose-induced apoptosis in Ad-MSCs, and Linc00324 contributed to the anti-apoptotic effect of GO. RIP and RNA pull-down confirmed that Linc00324 directly interacted with miR-7977, functioning as a miRNA sponge to regulate expression of the miR-7977 target gene STK4 (MST1) and downstream signaling pathways. In addition, GO reduced the apoptosis of Ad-MSCs in wounds and promoted wound healing. Taken together, these findings suggest GO may be a superior auxiliary material for Ad-MSCs to facilitate diabetic wound healing via the Linc00324/miR-7977/STK4 pathway.
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