Abstract

BackgroundIncreased apoptosis in adipose tissue-derived stem cells (ADSCs) limits their application in treating diabetes complications. Autophagy is a molecular process that allows cells to degrade and recover damaged macromolecules, and closely interacts with apoptosis. The aim of the present study was to investigate the potential role of autophagy in ADSC apoptosis induced by high glucose.MethodsHuman ADSCs were cultured in normal or high-glucose medium for 6 h, 12 h, or 24 h. The effects of high glucose on ADSC autophagy, reactive oxygen species (ROS) production, and apoptosis were evaluated. The impact of autophagy on ROS production and apoptosis was explored by treatment with rapamycin or 3-methyladenine (3-MA). The c-jun kinase (JNK) signaling pathway was investigated by pharmacological disruption of SP600125.ResultsADSCs subjected to high glucose stress showed an obvious induction of autophagy and apoptosis and a significant increase in intracellular ROS levels. The JNK signaling pathway was confirmed to be involved in high glucose-induced autophagy. Pre-treatment with SP600125 or N-acetylcysteine reversed the effects of high glucose on the JNK signaling pathway and autophagy-related proteins. Pretreatment of ADSCs with 3-MA under high glucose stress induced a further increase in ROS levels compared to those of high glucose-treated cells. Furthermore, ADSCs pretreated with 3-MA under high glucose stress showed a marked increase in apoptosis compared with that of the cells treated with high glucose. Conversely, pre-treatment with rapamycin inhibited the apoptosis of ADSCs.ConclusionsTaken together, our data suggest that autophagy may play a protective role in high glucose-induced apoptosis in ADSCs. ROS/JNK signaling is essential in upregulating high glucose-induced autophagy. This study provides new insights into the molecular mechanism of autophagy involved in high glucose-induced apoptosis in ADSCs.

Highlights

  • Increased apoptosis in adipose tissue-derived stem cells (ADSCs) limits their application in treating diabetes complications

  • We investigated the molecular mechanism of ADSC apoptosis and the changes in autophagic flux in high glucose-treated ADSCs to elucidate the role of autophagy in determining the fate of high glucose-treated ADSCs

  • These results suggest that targeting autophagy in ADSCs might be a potential therapeutic strategy for diabetes complications

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Summary

Introduction

Increased apoptosis in adipose tissue-derived stem cells (ADSCs) limits their application in treating diabetes complications. The aim of the present study was to investigate the potential role of autophagy in ADSC apoptosis induced by high glucose. Diabetes is a chronic disease that affects over 347 million people globally. Diabetic patients are very susceptible to a myriad of complications, such as chronic wounds, cardiovascular damage, kidney failure, and diabetic foot disease, which lead to both patient morbidity and mortality [3,4,5,6]. Increased apoptosis in stem cells limits their application in treating diabetes complications. A previous study demonstrated that high glucose results in the apoptosis of stem cells [10]. The intracellular mechanism of high glucose-induced ADSC apoptosis remains unclear

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