Abstract
Platelet-activating factor (PAF), protein kinase C (PKC)βI, transforming growth factor (TGF)‑β1 and aberrant extracellular matrix (ECM) deposition have been associated with diabetic nephropathy (DN). However, the mechanistic basis underlying this association remains to be elucidated. The present study investigated the association among the aforementioned factors in a DN model consisting of human mesangial cells (HMCs) exposed to high glucose (HG) and lysophosphatidylcholine (LPC) treatments. HMCs were divided into the following treatment groups: Control; PAF; PAF+PKCβI inhibitor LY333531; HG + LPC; PAF + HG + LPC; and PAF + HG + LPC + LY333531. Cells were cultured for 24 h, and PKCβI and TGF‑β1 expression was determined using the reverse transcription‑quantitative polymerase chain reaction and western blotting. The expression levels of the ECM‑associated molecules collagen IV and fibronectin in the supernatant were detected using ELISA analysis. Subcellular localization of PKCβI was assessed using immunocytochemistry. PKCβI and TGF‑β1 expression was increased in the PAF + HG + LPC group compared with the other groups (P<0.05); however, this effect was abolished in the presence of LY333531 (P<0.05). Supernatant fibronectin and collagen IV levels were increased in the PAF + HG + LPC group compared with the others (P<0.05); this was reversed by treatment with LY333531 (P<0.05). In cells treated with PAF, HG and LPC, PKCβI was translocated from the cytosol to the nucleus, an effect which was blocked when PKCβI expression was inhibited (P<0.05). The findings of the present study demonstrated that PAF stimulated ECM deposition in HMCs via activation of the PKC‑TGF‑β1 axis in a DN model.