MicroRNA-326-3p ameliorates high glucose and ox-LDL-IC- induced fibrotic injury in renal mesangial cells by targeting FcγRIII.

Aim: The aim of the present study was to identify the regulatory relationship between miR-326-3p and FcγRIII, and to explore the involvement of miR-326-3p/FcγRIII/TGF-β/Smad signalling pathway in fibrotic injury, which was induced by the high glucose (HG) and oxidized low density lipoprotein immune complex (ox-LDL-IC) in mouse glomerular mesangial cells (GMCs).

Methods: Dual-luciferase reporter system and real time PCR (RT-PCR) were used to identify FcγRIII as a target gene of miR-326-3p. Lentiviral transduction was used to construct different expression of miR-326-3p in GMCs, which were divided into three groups: miR-326-3p mimics group (miR-326-3p group), miR-326-3p inhibitor group (miR-326-3p-inhibit group) and scramble control group (control group). Then, each group was stimulated by normal glucose (NG), HG, ox-LDL-IC and HG + ox-LDL-IC, respectively. RT-PCR and western blot were used to measure the expressions of Col-I, CTGF, α-SMA, TGF-β, Smad2/3 and pSmad2/3.

Results: FcγRIII was regulated negatively by miR-326-3p in GMCs under the condition of HG and ox-LDL-IC, which implied FcγRIII as a target gene of miR-326-3p. Furthermore, compared with normal glucose group, the expressions of Col-I, CTGF, α-SMA, TGF-β and pSmad2/3 were higher under the condition of HG, ox-LDL-IC and HG + ox-LDL-IC (P < 0.05). In particular, miR-326-3p-inhibit groups exhibited the most significant increase (P < 0.05), while miR-326-3p could attenuate the increase (P < 0.05).

Conclusion: FcγRIII was identified as a target gene of miR-326-3p. MiR-326-3p/FcγRIII/TGF-β/Smad signaling pathway was investigated to be involved in the pathophysiology of renal fibrosis of DKD.