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Objective To observe glomerular mesangial cells (GMCs) proliferation induced by IgA1 and the association with the expression of apoptosis-related proteins-B cell lymphoma-2 (Bcl-2),cysteine aspartic acid protease-3 (Caspase-3),cysteine aspartic acid protease-9 (Caspase-9) and with mitofusin 2 (Mfn2) in rat GMCs,to study the possible mechanism of valsartan inhibiting rat GMCs proliferation,and to provide a new direction for the mechanism of GMCs proliferation and intervention research in IgA nephrology (IgAN).Methods GMCs stimulated with IgA1 were cultured in vitro to detect cellproliferation with the cell counting kit-8 cell activity assay (CCK8).GMCs were divided into three groups:CG,TG and VG.The GMCs proliferation level was detected by the CCK8,using real-time PCR to detect Mfn2 expression and Western blotting to detect protein levels of Mfn2,Bcl-2,Caspase-3,and Caspase-9.Results Rat GMCs proliferated significantly after stimulation with IgA1,and IgA1 could obviously stimulate high expression of Bcl-2 in GMCs and down regulate the expression of Mfn2,Caspase-3,and Caspase-9.Valsartan could inhibit the proliferation of GMCs induced by IgA1 significantly,downregulate the expression of Bcl-2,and upregulate the expression of Mfn2,Caspase-3,and Caspase-9.Conclusions These results showed that the mechanism of action of valsartan in the treatment of lgAN is inhibiting the proliferation of GMCs.This mechanism may be associated with the regulation of apoptosis-related proteins,such as Mfn2,Bcl-2,Caspase-3,and Caspase-9.These findings may provide a new direction for the mechanism of GMCs proliferation and intervention research in IgAN.
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ObjectiveThe purpose of this study was to investigate the clinical significance of HMGB1 and Smac/DIABLO protein expression in epithelial ovarian cancer.MethodsImmunohistochemistry (IHC) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining were used to detect the protein expression of HMGB1,Smac/DIABLO and cell apoptosis in 45 epithelial ovarian cancers by tissue microarray.ResultsThe protein expression of HMGB1 in epithelial ovarian cancers was significant higher than benign cancers and normal ovarian tissues( P ＜0.05).The protein expression of HMGB1 was related to the lymph node metastasis,which had a negative correlation with the cell apoptosis index ( rs =-0.583,P =0.000).The protein expression of Smac/DIABLO in epithelial ovarian cancers was significantly lower than benign cancers and normal ovarian tissues( P ＜0.05) ; the protein expression of HMGB1 in epithelial ovarian cancers had a negative relationship with protein expression of Smac/DIABLO( rs =-0.40,P =0.006).ConclusionsThe over-expression of HMGB1 in epithelial ovarian cancers may play an important part in the metastasis of the epithelial ovarian cancers.The over-expression of HMGB1 and the low-expression of Smac/DIABLO may take part in the occurrence and development of the epithelial ovarian cancers through abnormal cell apoptosis.