Mesenchymal stem ceils （MSCs） have been demonstrated to have promising therapeutic benefits for a variety of neurological dis- eases; however, the underlying mechanisms are poorly understood. Here, we showed that in...Mesenchymal stem ceils （MSCs） have been demonstrated to have promising therapeutic benefits for a variety of neurological dis- eases; however, the underlying mechanisms are poorly understood. Here, we showed that intravitreal infusion of MSCs promoted retinal ganglion cell （RGC） survival in a mouse model of acute glaucoma, with significant inhibition of microglial activation, production of TNF-α, IL-1β, and reactive oxygen species, as well as caspase-8 and caspase-3 activation. In vitro, MSCs inhibited both caspase-8-mediated RGC apoptosis and microgUal activation, partly via the action of stanniocalcin 1 （STCl）. Furthermore, we found that microRNA-21a-Sp （miR-21） and its target, PDCD4, were essential for STC1 production and the neuroprotective property of MSCs in vitro and in vivo. Importantly, miR-21 overexpression or PDCD4 knockdown augmented MSC-mediated neuroprotective effects on acute glaucoma. These data highlight a previously unrecognized neuroprotective mechanism by which the miR-21/ PDCD4 axis induces MSCs to secrete STC1 and other factors that exert neuroprotective effects. Therefore, modulating the miR- 21/PDCD4 axis might be a promising strategy for clinical treatment of acute glaucoma and other neurological diseases.展开更多
Journal of Molecular Cell Biology(2017),9(4),289‒301,https://doi.org/10.1093/jmcb/mjx022 In this article,there were errors in Figures 4D(western blotting analysis),3E and F,5G and H,and 5J and K(flow cytometry analysi...Journal of Molecular Cell Biology(2017),9(4),289‒301,https://doi.org/10.1093/jmcb/mjx022 In this article,there were errors in Figures 4D(western blotting analysis),3E and F,5G and H,and 5J and K(flow cytometry analysis).Iba1 band in Figure 4D was the same as Cleaved caspase-3 band in Figure 2F.This was caused by carelessly mistaking the latter(Cleaved caspase-3,#1)for Iba1 band due to the high similarity between images(raw blot images of these bands from three experiments are provided in the Supplementary material).The corrected Figure 4D with updated Iba1 band(#1)and quantitation graph is shown below.展开更多
Necroptosis is currently attracting the attention of the scientific community for its broad implications in in-flammatory diseases and cancer.However,detecting ongoing necroptosis in vivo under both experimental and c...Necroptosis is currently attracting the attention of the scientific community for its broad implications in in-flammatory diseases and cancer.However,detecting ongoing necroptosis in vivo under both experimental and clinical disease conditions remains challenging.The technical barrier lies in four aspects,namely tissue sam-pling,real-time in vivo monitoring,specific markers,and distinction between different types of cell death.In this review,we presented the latest methodological advances for in vivo necroptosis identification.The advances highlighted the multi-parameter flow cytometry,sA5-YFP tool,radiolabeled Annexin V/Duramycin,Gallium-68-labeled IRDye800CW contrast agent,and SMART platform in vivo.We also discussed the up-to-date research mod-els in studying necroptosis,particularly the mice models for manipulating and monitoring necroptosis.Based on these recent advances,this review aims to provide some advice on current necroptosis techniques and approaches.展开更多
基金This study was partially supported by the Natural Science Foundation of China （81470627 and 81670897）, key projects from the Natural Science Foundation of Guangdong Province （201_4A030308005）, and Guangdong Natural Science Funds for Distinguished Young Scholar （2016A030306006）.
文摘Mesenchymal stem ceils （MSCs） have been demonstrated to have promising therapeutic benefits for a variety of neurological dis- eases; however, the underlying mechanisms are poorly understood. Here, we showed that intravitreal infusion of MSCs promoted retinal ganglion cell （RGC） survival in a mouse model of acute glaucoma, with significant inhibition of microglial activation, production of TNF-α, IL-1β, and reactive oxygen species, as well as caspase-8 and caspase-3 activation. In vitro, MSCs inhibited both caspase-8-mediated RGC apoptosis and microgUal activation, partly via the action of stanniocalcin 1 （STCl）. Furthermore, we found that microRNA-21a-Sp （miR-21） and its target, PDCD4, were essential for STC1 production and the neuroprotective property of MSCs in vitro and in vivo. Importantly, miR-21 overexpression or PDCD4 knockdown augmented MSC-mediated neuroprotective effects on acute glaucoma. These data highlight a previously unrecognized neuroprotective mechanism by which the miR-21/ PDCD4 axis induces MSCs to secrete STC1 and other factors that exert neuroprotective effects. Therefore, modulating the miR- 21/PDCD4 axis might be a promising strategy for clinical treatment of acute glaucoma and other neurological diseases.
文摘Journal of Molecular Cell Biology(2017),9(4),289‒301,https://doi.org/10.1093/jmcb/mjx022 In this article,there were errors in Figures 4D(western blotting analysis),3E and F,5G and H,and 5J and K(flow cytometry analysis).Iba1 band in Figure 4D was the same as Cleaved caspase-3 band in Figure 2F.This was caused by carelessly mistaking the latter(Cleaved caspase-3,#1)for Iba1 band due to the high similarity between images(raw blot images of these bands from three experiments are provided in the Supplementary material).The corrected Figure 4D with updated Iba1 band(#1)and quantitation graph is shown below.
文摘Necroptosis is currently attracting the attention of the scientific community for its broad implications in in-flammatory diseases and cancer.However,detecting ongoing necroptosis in vivo under both experimental and clinical disease conditions remains challenging.The technical barrier lies in four aspects,namely tissue sam-pling,real-time in vivo monitoring,specific markers,and distinction between different types of cell death.In this review,we presented the latest methodological advances for in vivo necroptosis identification.The advances highlighted the multi-parameter flow cytometry,sA5-YFP tool,radiolabeled Annexin V/Duramycin,Gallium-68-labeled IRDye800CW contrast agent,and SMART platform in vivo.We also discussed the up-to-date research mod-els in studying necroptosis,particularly the mice models for manipulating and monitoring necroptosis.Based on these recent advances,this review aims to provide some advice on current necroptosis techniques and approaches.
