Metformin prevents nephrolithiasis formation by inhibiting the expression of OPN and MCP-1 invitro and invivo.

Abstract

Treatment targeting osteopontin (OPN) and monocyte chemoattractant protein 1 (MCP-1) has been recognized as a novel approach in renal crystal formation. The present study was designed to investigate the suppressive effects of metformin on nephrolithiasis formation and its potential mechanism. The cytotoxicity of metformin on MDCK and HK-2 cells was determined using a Cell Counting Kit-8 assay in vitro. Subsequently, the mRNA transcription and protein expression levels of MCP-1 and OPN were detected by reverse transcription-quantitative-polymerase chain reaction analysis, western blot analysis and ELISA. Male Sprague-Dawley rats were divided into a control group, ethylene glycol (EG) group and EG + metformin group. The expression levels of MCP-1 and OPN and crystal formations were evaluated in renal tissues following an 8-week treatment period. In vitro, metformin significantly inhibited the production of MCP-1 and OPN induced by oxalate at the mRNA and protein expression levels. In vivo, increased expression levels of MCP-1 and OPN were detected in the EG group compared with the controls, and this upregulation was reversed in the EG + metformin group. Renal crystal deposition in the EG + metformin group was markedly decreased compared with that in the EG group. Therefore, the results of the study suggest that metformin suppressed urinary crystal deposit formation, possibly by mediating the expression of inflammatory mediators OPN and MCP-1.