Aim: To investigate the effects and mechanism of losartan on expression of CTGF induced by high glucose.
Methods: Mouse mesangial cells (MMCs) were cultured in vitro, initially, MMCs were stimulated by high glucose(25 mmol/L glucose) for 24 h, 48 h, 72 h, the phosphorylation of ERK1/2 was assessed by Western blot. Then MMCs were randomly divided into 5 groups: (1) Low glucose group (5.6 mmol/L glucose); (2)Sorbitol group (5.6 mmol/L glucose + 19.4 mmol/L sorbitol); (3) High glucose group (25 mmol/L glucose); (4) Losartan group (25 mmol/L glucose + 10(5) mol/L losartan); (5) ERK inhibitors group (25 mmol/L glucose + 25 micromol/L PD98059). After 48 hours, the phosphorylation of ERK1/2 were detected by Western blot. After 72 hours, the protein and mRNA expression level of CTGF were assessed by Western blot and real-time PCR.
Results: High glucose induced the phosphorylation of ERK1/2 in a time-dependent manner. The protein expression of phosphor-ERK1/2 and CTGF were increased in high glucose group comparing with low glucose group(P<0.01), and reduced in losartan group and ERK inhibitors group comparing with high glucose group(P<0.05). The mRNA expression of CTGF was increased in high glucose group comparing with low glucose group(P<0.01) , and reduced in losartan group and ERK inhibitors group comparing with high glucose group(P<0.01).
Conclusion: Losartan can inhibit high glucose-induced CTGF expression in mouse mesangial cells, and the mechanisms maybe involve the interruption of ERK1/2 MAPK pathway.