AMPK promotes survival and adipogenesis of ischemia-challenged ADSCs in an autophagy-dependent manner |
| |
Authors: | Chichi Li Kewei Chen Minghui Jia Xi Ding Zipei Jiang Liqun Li Dan Zhang |
| |
Institution: | 1. Plastic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, PR China;2. Otolaryngology Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, PR China;3. Department of Stomatology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, PR China;4. Department of Ophthalmology, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, PR China;5. Department of Respiratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang, Wenzhou City, Zhejiang Province 325000, PR China |
| |
Abstract: | Some studies have shown that transplanted fat tissues usually cannot survive for long if adipose-derived stem cells (ADSCs) are removed from the tissues in advance. It is more meaningful to explore the mechanism mediating survival and differentiation of ADSCs in the transplanted microenvironment. AMP-activated protein kinase (AMPK) has been shown to be one of the energy receptors that regulate many aspects of cellular metabolism. AMPK activation has been implicated in models of adult ischemic injury, but the mechanism and the regulating effects of AMPK on survival and adipogenesis of transplanted ADSCs are still little known. In this study, we simulated the transplanted microenvironment using oxygen-glucose deprivation (OGD) to test the survival and adipogenesis of ADSCs. We found that OGD treatment triggered significant apoptosis and promoted autophagy. Simultaneously, OGD hindered the differentiation of ADSCs into mature adipocytes. After inhibiting AMPK, the OGD-induced apoptosis rate increased but autophagy was inhibited. The adipogenesis level also decreased. To show that the effects of AMPK on apoptosis and adipogenesis were autophagy-dependent, we pre-inhibited or pre-promoted autophagy with siATG7 or rapamycin while blocking AMPK. We found that inhibiting or improving autophagy exacerbated or alleviated the role of AMPK prohibition in apoptosis and adipogenesis. Furthermore, we showed that AMPK inhibition significantly lowered ULK1 activity but promoted mTOR activity, so that to inhibit autophagy. Our study shows that AMPK plays a protective role in maintaining survival and adipogenesis of OGD-challenged ADSCs partly by positively regulating autophagy. AMPK positively regulates autophagy by inhibiting mTOR but promoting ULK1 activity in OGD condition. |
| |
Keywords: | AMPK AMP-activated protein kinase ADSCs adipose-derived stem cells OGD oxygen-glucose deprivation mTOR mammalian target of rapamycin BML-275 Dorsomorphin PPARγ peroxisome proliferator-activated receptor gamma C/EBP CCAAT/enhancer binding protein LC3 microtubule-associated protein 1-light chain 3 p62 protein 62 ATG autophagy-related genes ULK1 Unc-51 like autophagy activating kinase Adipose-derived stem cells Adipogenesis Ischemia Autophagy AMP-activated protein kinase |
本文献已被 ScienceDirect 等数据库收录! |
|