RESUMEN
Aim To investigate the effect of CMHX008, a novel peroxisome proliferator-activated receptor γ (PPARγ) partial agonist, on fibrogenic pathways and its potential mechanism in renal tubular epithelial HK-2 cells in comparison with rosiglitazone. Methods HK-2 cells were cultured with 30 mmol . L 1 D-(+)-glucose, and then treated with rosiglitazone and CMHX008. Cell counting kit-8(CCK-8) was used to detect cell viability; immunoblotting was used to detect protein expression fibrogenic markers and p-PPARγ(ser273) in HK-2 cells; quantitative real time PCR (qRT-PCR) was used to detect fibrosis-related mRNA levels; wound healing assay and transwell assay were used to detect the migration and invasion ability of HK-2 cells. Results CCK-8 analysis showed that 3 (imol . L 1 rosiglitazone and 3 μmol . L 1 CMHX008 had no obvious cytotoxicity to HK-2 cells; immunoblotting revealed that rosiglitazone and CMHX008 could reverse the up-regulation of p-PPARγ(ser273), reduce transforming growth factor β1 (TGF-β1) and α-smooth muscle actin(α-SMA) protein levels, and up-regulate E-cadherin protein expression levels in HK-2 cells in high glucose conditions; wound healing assay and transwell assay showed that rosiglitazone and CMHX008 could inhibit the increase of migration and invasion ability of hyperglycemia-cultured HK-2 cells. Conclusions The novel PPAR7 agonist CMHX008 can improve hyperglycemia-induced renal tubular fibrosis, which may be possibly related to the inhibition of p-PPARγ(Ser273) phosphorylation.