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Updated: Apr 12, 2026

In Situ Immunofluorescent Staining of Autophagy in Muscle Stem Cells
Published on: June 12, 2017
High glucose induces bone marrow-derived mesenchymal stem cell senescence by upregulating autophagy
Tzu-Ching Chang1, Min-Fen Hsu2, Kenneth K Wu3
1Metabolomic Medicine Research Center, China Medical University Hospital, Taichung, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Abstract:
Hyperglycemia was reported to cause bone marrow hematopoietic niche dysfunction, and high glucose (HG) in the cultured medium induces MSC senescence. The underlying mechanism is unclear. Here, we investigated the role of HG-induced autophagy in bone-marrow-derived mesenchymal stem cell (BMSC) senescence. HG (25 mM) increased expression of Beclin-1, Atg 5, 7 and 12, generation of LC3-II and autophagosome formation which was correlated with development of cell senescence. Pretreatment of HG-MSC with 3-methyladenine (3-MA) prevented senescence but increased apoptosis. N-acetylcysteine (NAC) was effective in abrogating HG-induced autophagy accompanied by prevention of senescence. Diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase, blocked autophagy and senescence in a manner comparable to NAC. 3-MA, NAC and DPI inhibited HG-induced interleukin-6 production in BMSCs. These results suggest that hyperglycemia induces MSC senescence and local inflammation via a novel oxidant-mediated autophagy which contributes to bone marrow niche dysfunction and hematopoietic impairment.
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