Expression of mitofusin 2 in IgA1-induced glomerular mesangial cell proliferation and association with a valsartan-induced inhibitory effect on hyperplasia

Abstract

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 cell proliferation 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 IgAN 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. Key words: Mitochondrial proteins/ME; Mesangial cells/PA/ME; Immunoglobulin A/AE; Valine/AA/PD