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. 相似文献
Due to a long-term transgression since the Early Cambrian, an extensive shallow-water carbonate platform was developed in the entire Tarim Basin (NW China). During the deposition of the Yingshan Formation (Early-Middle Ordovician), a carbonate ramp system was formed in the intrashelf basin in the Bachu-Keping area of the western basin. Four well-exposed outcrop sections were selected to investigate their depositional facies, cycles, and sequences, as well as the depositional evolution. Detailed facies analyses permit the recognition of three depositional facies associations, including peritidal, semi-restricted subtidal, and open-marine subtidal facies, and eleven types of lithofacies. These are vertically arranged into meter-scale, shallowing-upward peritidal, semi-restricted subtidal, and open-marine subtidal cycles, in the span of Milankovitch frequency bands, suggesting a dominant control of Earth’s orbital forcing on the cyclic sedimentation on the platform. On the basis of vertical facies (or lithofacies) and cycle stacking patterns, as well as accommodation changes illustrated graphically by Fischer plots at all studied sections, six third-order depositional sequences are recognized and consist of lower transgressive and upper regressive parts. In shallow depositional settings, the transgressive packages are dominated by thicker-than-average, shallow subtidal cycles, whereas the regressive parts are mainly represented by thinner-than-average, relatively shallow subtidal to peritidal cycles. In relatively deep environments, however, the transgressive and regressive successions display the opposite trends of cycle stacking patterns, i.e., thinner-than-average subtidal cycles of transgressive packages. Sequence boundaries are mainly characterized by laterally traceable, transitional zones without apparent subaerial exposure features. Good correlation of the long-term changes in accommodation space inferred from vertical facies and cycle stacking patterns with sea-level fluctuations elsewhere around the world suggests an overriding eustatic control on cycle origination, platform building-up and evolution during the Early-Middle Ordovician, although with localized influences of syndepositional faulting and depositional settings. 相似文献
Transgenic and knockout animal models are widely used to investigate the role of receptors, signaling pathways, and other peptides and proteins. Varying results are often published on the same model from different groups, and much effort has been put into understanding the underlying causes of these sometimes conflicting results. Recently, it has been shown that a P2X4R knockout model carries a so-called passenger mutation in the P2X7R gene, potentially affecting the interpretation of results from studies using this animal model. We therefore report this case to raise awareness about the potential pitfalls using genetically modified animal models, especially within P2 receptor research. Although purinergic signaling has been recognized as an important contributor to the regulation of bone remodeling, the process that maintains the bone quality during life, little is known about the role of the P2X4 receptor (P2X4R) in regulation of bone remodeling in health and disease. To address this, we analyzed the bone phenotype of P2rx4tm1Rass (C57BL/6J) knockout mice and corresponding wildtype using microCT and biomechanical testing. Overall, we found that the P2X4R knockout mice displayed improved bone microstructure and stronger bones in an age- and gender-dependent manner. While cortical BMD, trabecular BMD, and bone volume were higher in the 6-month-old females and 3-month-old males, this was not the case for the 3-month-old females and the 6-month-old males. Bone strength was only affected in the females. Moreover, we found that P2X4R KO mice carried the P2X7 receptor 451P wildtype allele, whereas the wildtype mice carried the 451L mutant allele. In conclusion, this study suggests that P2X4R could play a role in bone remodeling, but more importantly, it underlines the potential pitfalls when using knockout models and highlights the importance of interpreting results with great caution. Further studies are needed to verify any specific effects of P2X4R on bone metabolism.
