Xiaokeping-containing serum suppresses high-glucose-induced proliferation of mesangial cells involved in the regulation of cell cycle progression and the p38 mitogen-activated protein kinase pathway.

Abstract

To investigate the efficacy of Xiaokeping (XKP)-containing serum on the proliferation of high-glucose-induced mesangial cells (MCs) and the potential underlying mechanism. XKP-containing serum was prepared by the intragastric administration of XKP in rats. HBZY-1 cells were cultured with normal glucose (NC group), high glucose (HG group), and high glucose with different XKP concentrations. Cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the cell cycle distribution was detected by flow cytometry. The expression of p38 mitogen-activated protein kinase (p38MAPK) pathway components in MCs was detected by Western blotting and quantitative real-time polymerase chain reaction. The MC proliferation level in the high-glucose group was significantly higher than that in the normal control group, and XKP suppressed the HG-induced proliferation of MCs dose dependently. Moreover, flow cytometry revealed that XKP blocked cell cycle progression by inducing cell cycle arrest in G1 phase and inhibiting S phase entry. XKP down-regulated the protein and mRNA expression of p38MAPK in MCs (P < 0.05 vs HG). The present study demonstrated that XKP-containing serum inhibits high-glucoseinduced proliferation of MCs by causing cell cycle arrest at G1 phase and inhibiting S phase entry. The underlying mechanism involves the down-regulation of the p38MAPK signaling pathway, providing a theoretical basis for the use of XKP to treat diabetic kidney disease.