Atorvastatin prevents glomerular extracellular matrix formation by interfering with the PKC signaling pathway

Platelet-activating factor (PAF) promotes glomerular extracellular matrix (ECM) deposition, primarily through activation of the protein kinase C (PKC) pathway. The present study was designed to investigate whether atorvastatin, which mediates a protective effect against glomerular ECM deposition and diabetic neuropathy, may interfere with the PKC-transforming growth factor-beta 1 (TGF-beta 1) pathway in a model of human mesangial cells (HMCs) exposed to a high glucose (HG) and lysophosphatidylcholine (LPC) environment. HMCs were divided into three treatment groups: Control, high glucose and lysophosphatidylcholine (HG+LPC), and HG+LPC+atorvastatin. Cells were cultured for 24 h. The levels of the ECM-associated molecules collagen IV (Col IV) and fibronectin (Fn) in the supernatant were detected using an ELISA kit. PKC-beta 1, TGF-beta 1 and PAF-receptor gene expression was detected by reverse transcription-quantitative polymerase chain reaction. PKC-beta 1 and TGF-beta 1 protein expression was detected by western blotting, and the subcellular localization of PKC-beta 1 was assessed using immunofluorescence. The results indicated that atorvastatin may reduce the secretion of ECM components (Fn and Col IV) in HMCs in a HG and LPC environment, by inhibiting the increase in PAF secretion and the activation of the PKC-TGF-beta 1 signaling pathway.