AIM： To determine the role of microRNA （miRNA）-29a and miRNA-29c in the regulation of apoptosis in early rat diabetic cataract formation.METHODS： Streptozotocin （STZ）-induced diabetic Sprague-Dawley （SD） rats ...AIM： To determine the role of microRNA （miRNA）-29a and miRNA-29c in the regulation of apoptosis in early rat diabetic cataract formation.METHODS： Streptozotocin （STZ）-induced diabetic Sprague-Dawley （SD） rats were used in the study. The expression level of miRNA-29a, miRNA-29c, and BCL2-modifying factor （BMF） in lens epithelial cells （LECs） samples were measured using quantitative real-time polymerase chain reaction. Prediction algorithms of miRanda, TargetScan 6.2, and mirRDB to perform a miRNA gene network analysis were used for the potential miRNA-29a and miRNA-29c targets. RESULTS： The miRNA-29a and miRNA-29c expression levels were all significantly lower in the control group compared to the 2 and 4wk diabetic samples （P〈0.01）. The network analysis indicated that one miRNA-29a and miRNA-29c targets was BMF. There was significantly higher expression of BMF mRNA compared to the normal controls （P〈0.01）. CONCLUSION： Apoptosis occurs in rat LECs following high blood glucose exposure. It is likely that apoptosis during diabetic cataract formation involves the decreased expression of miRNA-29a and miRNA-29c and the increased expression of BMF.展开更多
Background Left ventricular(LV)remodeling is the most common target organ damage in hypertension.Previously,our study found that plasma microRNA-29a(miR-29a)level was associated with the LV remodeling in hypertensive ...Background Left ventricular(LV)remodeling is the most common target organ damage in hypertension.Previously,our study found that plasma microRNA-29a(miR-29a)level was associated with the LV remodeling in hypertensive patients.However,the causal relationship between miR-29a and LV remodeling remains unknown.Thus,the aim of this study was to investigate the regulation mechanism of miR-29a in LV remodeling.Methods&Results Overexpression and knockdown miR-29a mice were generated by tail-intravenous injection of miR-29a-mimic and inhibitor lentivirus for one week respectively.Then the mice were subjected to angiotensin-II(AngII)induced LV remodeling by subcutaneous AngII capsule osmotic pumping into AngII for four weeks.AngII-induced LV remodeling mice as the model group(n=9).Age-matched male SPF C57/BL6J mice(6–8 weeks old)were treated with the pumping of saline as a vehicle(n=6).In vivo,overexpression miR-29a ameliorated AngII-induced LV remodeling,while knockdown miR-29a deteriorated LV remodeling.Simultaneously,we observed that overexpression miR-29a mice inhibited but knockdown miR-29a mice increased cardiac cross-sectional area,indicating that miR-29a has an antagonistic effect on cardiac hypertrophy.Further studies found that overexpression miR-29a inhibited the content of the LV collagen including collagen I and III.Moreover,the expression of transforming growth factor-β(TGF-β)and phosphorylated SMAD2/3 decreased with the down-regulation of collagen I and III in overexpression miR-29a mice.Conclusions Our finding indicates that overexpression miR-29a attenuates LV remodeling by inhibiting collagen deposition,TGF-β,and phosphorylated SMAD2/3 expression.Thus,intervention miR-29a may be a therapeutic target for attenuating LV remodeling.展开更多
文摘AIM： To determine the role of microRNA （miRNA）-29a and miRNA-29c in the regulation of apoptosis in early rat diabetic cataract formation.METHODS： Streptozotocin （STZ）-induced diabetic Sprague-Dawley （SD） rats were used in the study. The expression level of miRNA-29a, miRNA-29c, and BCL2-modifying factor （BMF） in lens epithelial cells （LECs） samples were measured using quantitative real-time polymerase chain reaction. Prediction algorithms of miRanda, TargetScan 6.2, and mirRDB to perform a miRNA gene network analysis were used for the potential miRNA-29a and miRNA-29c targets. RESULTS： The miRNA-29a and miRNA-29c expression levels were all significantly lower in the control group compared to the 2 and 4wk diabetic samples （P〈0.01）. The network analysis indicated that one miRNA-29a and miRNA-29c targets was BMF. There was significantly higher expression of BMF mRNA compared to the normal controls （P〈0.01）. CONCLUSION： Apoptosis occurs in rat LECs following high blood glucose exposure. It is likely that apoptosis during diabetic cataract formation involves the decreased expression of miRNA-29a and miRNA-29c and the increased expression of BMF.
基金supported by the National Natural Science Foundation of China(No.81570383)
文摘Background Left ventricular(LV)remodeling is the most common target organ damage in hypertension.Previously,our study found that plasma microRNA-29a(miR-29a)level was associated with the LV remodeling in hypertensive patients.However,the causal relationship between miR-29a and LV remodeling remains unknown.Thus,the aim of this study was to investigate the regulation mechanism of miR-29a in LV remodeling.Methods&Results Overexpression and knockdown miR-29a mice were generated by tail-intravenous injection of miR-29a-mimic and inhibitor lentivirus for one week respectively.Then the mice were subjected to angiotensin-II(AngII)induced LV remodeling by subcutaneous AngII capsule osmotic pumping into AngII for four weeks.AngII-induced LV remodeling mice as the model group(n=9).Age-matched male SPF C57/BL6J mice(6–8 weeks old)were treated with the pumping of saline as a vehicle(n=6).In vivo,overexpression miR-29a ameliorated AngII-induced LV remodeling,while knockdown miR-29a deteriorated LV remodeling.Simultaneously,we observed that overexpression miR-29a mice inhibited but knockdown miR-29a mice increased cardiac cross-sectional area,indicating that miR-29a has an antagonistic effect on cardiac hypertrophy.Further studies found that overexpression miR-29a inhibited the content of the LV collagen including collagen I and III.Moreover,the expression of transforming growth factor-β(TGF-β)and phosphorylated SMAD2/3 decreased with the down-regulation of collagen I and III in overexpression miR-29a mice.Conclusions Our finding indicates that overexpression miR-29a attenuates LV remodeling by inhibiting collagen deposition,TGF-β,and phosphorylated SMAD2/3 expression.Thus,intervention miR-29a may be a therapeutic target for attenuating LV remodeling.
