Dual specificity phosphatase 22 suppresses mesangial cell hyperproliferation, fibrosis, inflammation and the MAPK signaling pathway in diabetic nephropathy.

Abstract

Dual specificity phosphatase 22 (DUSP22) regulates fibrosis and inflammation, which may be implicated in the development of diabetic nephropathy (DN). Hence, the current study aimed to assess the effect of DUSP22 on cell proliferation, apoptosis, fibrosis and inflammation in mouse mesangial cell line (SV40-MES13) under both high glucose (HG) and low glucose (LG) conditions. SV40-MES13 cells were treated with HG and LG, then HG-group cells were transfected with DUSP22 overexpression and control plasmids, meanwhile LG-group cells were transfected with DUSP22 and control siRNAs. Then, cell proliferation using Cell Counting Kit-8, cell apoptosis by TUNEL assay, protein expression using western blotting, inflammatory cytokines using ELISA and RNA using reverse transcription-quantitative PCR were determined. DUSP22 mRNA and protein were decreased in SV40-MES13 cells under the HG condition compared with those under the LG condition. Under the HG condition, DUSP22 overexpression suppressed SV40-MES13 cell proliferation at 48 and 72 h as well as Bcl2, but it facilitated TUNEL-reflected apoptotic rate and cleaved-caspase-3; besides, DUSP22 overexpression restrained proteins of fibronectin 1, collagen I, transforming growth factor beta 1, and their corresponding mRNAs. As to the inflammation, DUSP22 overexpression downregulated TNF-α, IL-1β, IL-6 and IL-12 under the HG condition. By contrast, DUSP22 siRNA promoted SV40-MES13 cell proliferation, fibrosis and inflammation, but attenuated apoptosis in SV40-MES13 cells under the LG condition. Additionally, DUSP22 overexpression inactivated phosphorylated (p)-ERK, p-JNK, and p-P38 in HG-treated SV40-MES13 cells; differently, DUSP22 small interfering RNA facilitated them under the LG condition. In conclusion, DUSP22 suppresses HG-induced mesangial cell hyperproliferation, fibrosis, inflammation and the MAPK pathway, implying its potency in DN treatment.