BACKGROUND Recent studies have demonstrated that mesenchymal stem cells(MSCs)can rescue injured target cells via mitochondrial transfer.However,it has not been fully understood how bone marrow-derived MSCs repair glom...BACKGROUND Recent studies have demonstrated that mesenchymal stem cells(MSCs)can rescue injured target cells via mitochondrial transfer.However,it has not been fully understood how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease(DKD).AIM To explore the mitochondrial transfer involved in the rescue of injured glomerular endothelial cells(GECs)by MSCs,both in vitro and in vivo.METHODS In vitro experiments were performed to investigate the effect of co-culture with MSCs on high glucose-induced GECs.The transfer of mitochondria was visualized using fluorescent microscopy.GECs were freshly sorted and ultimately tested for apoptosis,viability,mRNA expression by real-time reverse transcriptase-polymerase chain reaction,protein expression by western blot,and mitochondrial function.Moreover,streptozotocin-induced DKD rats were infused with MSCs,and renal function and oxidative stress were detected with an automatic biochemical analyzer and related-detection kits after 2 wk.Kidney histology was analyzed by hematoxylin and eosin,periodic acid-Schiff,and immunohistochemical staining.RESULTS Fluorescence imaging confirmed that MSCs transferred mitochondria to injured GECs when cocultured in vitro.We found that the apoptosis,proliferation,and mitochondrial function of injured GECs were improved following co-culture.Additionally,MSCs decreased pro-inflammatory cytokines[interleukin(IL)-6,IL-1β,and tumor necrosis factor-α]and pro-apoptotic factors(caspase 3 and Bax).Mitochondrial transfer also enhanced the expression of superoxide dismutase 2,B cell lymphoma-2,glutathione peroxidase(GPx)3,and mitofusin 2 and inhibited reactive oxygen species(ROS)and dynamin-related protein 1 expression.Furthermore,MSCs significantly ameliorated functional parameters(blood urea nitrogen and serum creatinine)and decreased the production of malondialdehyde,advanced glycation end products,and ROS,whereas they increased the levels of GPx and superoxide dismutase in vivo.In addition,significant reductions in the glomerular basement membrane and renal interstitial fibrosis were observed following MSC treatment.CONCLUSION MSCs can rejuvenate damaged GECs via mitochondrial transfer.Additionally,the improvement of renal function and pathological changes in DKD by MSCs may be related to the mechanism of mitochondrial transfer.展开更多
Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperla...Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondriatargeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications.展开更多
目的探讨肿瘤细胞凋亡过程中survivin-2B的作用机制。方法通过流式细胞仪分析survivin-2B对肿瘤细胞周期的影响;利用激光共聚焦显微镜观察通过青色荧光蛋白(CFP)标记的survivin-2B和罗丹明123标记的线粒体在细胞内的定位及在细胞凋亡过...目的探讨肿瘤细胞凋亡过程中survivin-2B的作用机制。方法通过流式细胞仪分析survivin-2B对肿瘤细胞周期的影响;利用激光共聚焦显微镜观察通过青色荧光蛋白(CFP)标记的survivin-2B和罗丹明123标记的线粒体在细胞内的定位及在细胞凋亡过程中的变化;采用荧光共振能量转移(fluorescence resonance energy transfer,FRET)方法分析survivin-2B和survivin-ΔEx3在细胞内的相互作用。结果流式细胞仪分析结果表明,Survivin-2B能够明显抑制肿瘤细胞生长,促使细胞凋亡增加;通过激光共聚焦显微镜观察到凋亡早期survivin-2B聚集在细胞发生固缩的部位,且在肿瘤凋亡过程中不存在明显的线粒体定位及与线粒体的相关性;FRET分析显示survivin-2B与survivin-ΔEx3在细胞质中存在很弱的相互作用。结论Survivin-2B能够明显促进肿瘤细胞凋亡,且survivin-2B通过与survivin-ΔEx3直接结合以阻断其抗凋亡效应的可能性较小。展开更多
基金Supported by the Science and Technology Foundation of Jinhua,No.2021-4-190.
文摘BACKGROUND Recent studies have demonstrated that mesenchymal stem cells(MSCs)can rescue injured target cells via mitochondrial transfer.However,it has not been fully understood how bone marrow-derived MSCs repair glomeruli in diabetic kidney disease(DKD).AIM To explore the mitochondrial transfer involved in the rescue of injured glomerular endothelial cells(GECs)by MSCs,both in vitro and in vivo.METHODS In vitro experiments were performed to investigate the effect of co-culture with MSCs on high glucose-induced GECs.The transfer of mitochondria was visualized using fluorescent microscopy.GECs were freshly sorted and ultimately tested for apoptosis,viability,mRNA expression by real-time reverse transcriptase-polymerase chain reaction,protein expression by western blot,and mitochondrial function.Moreover,streptozotocin-induced DKD rats were infused with MSCs,and renal function and oxidative stress were detected with an automatic biochemical analyzer and related-detection kits after 2 wk.Kidney histology was analyzed by hematoxylin and eosin,periodic acid-Schiff,and immunohistochemical staining.RESULTS Fluorescence imaging confirmed that MSCs transferred mitochondria to injured GECs when cocultured in vitro.We found that the apoptosis,proliferation,and mitochondrial function of injured GECs were improved following co-culture.Additionally,MSCs decreased pro-inflammatory cytokines[interleukin(IL)-6,IL-1β,and tumor necrosis factor-α]and pro-apoptotic factors(caspase 3 and Bax).Mitochondrial transfer also enhanced the expression of superoxide dismutase 2,B cell lymphoma-2,glutathione peroxidase(GPx)3,and mitofusin 2 and inhibited reactive oxygen species(ROS)and dynamin-related protein 1 expression.Furthermore,MSCs significantly ameliorated functional parameters(blood urea nitrogen and serum creatinine)and decreased the production of malondialdehyde,advanced glycation end products,and ROS,whereas they increased the levels of GPx and superoxide dismutase in vivo.In addition,significant reductions in the glomerular basement membrane and renal interstitial fibrosis were observed following MSC treatment.CONCLUSION MSCs can rejuvenate damaged GECs via mitochondrial transfer.Additionally,the improvement of renal function and pathological changes in DKD by MSCs may be related to the mechanism of mitochondrial transfer.
基金supported by grants from the National Natural Science Foundation of China(No.81730057,81501698)the National Key Research and Development Program of China(No.2017YFC11003302)the Shenzhen San-ming Project(No.SZSM20162011)
文摘Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondriatargeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications.
文摘目的探讨肿瘤细胞凋亡过程中survivin-2B的作用机制。方法通过流式细胞仪分析survivin-2B对肿瘤细胞周期的影响;利用激光共聚焦显微镜观察通过青色荧光蛋白(CFP)标记的survivin-2B和罗丹明123标记的线粒体在细胞内的定位及在细胞凋亡过程中的变化;采用荧光共振能量转移(fluorescence resonance energy transfer,FRET)方法分析survivin-2B和survivin-ΔEx3在细胞内的相互作用。结果流式细胞仪分析结果表明,Survivin-2B能够明显抑制肿瘤细胞生长,促使细胞凋亡增加;通过激光共聚焦显微镜观察到凋亡早期survivin-2B聚集在细胞发生固缩的部位,且在肿瘤凋亡过程中不存在明显的线粒体定位及与线粒体的相关性;FRET分析显示survivin-2B与survivin-ΔEx3在细胞质中存在很弱的相互作用。结论Survivin-2B能够明显促进肿瘤细胞凋亡,且survivin-2B通过与survivin-ΔEx3直接结合以阻断其抗凋亡效应的可能性较小。
