| First Author | Han X | Year | 2021 |
| Journal | Exp Cell Res | Volume | 407 |
| Issue | 2 | Pages | 112753 |
| PubMed ID | 34499887 | Mgi Jnum | J:312964 |
| Mgi Id | MGI:6792507 | Doi | 10.1016/j.yexcr.2021.112753 |
| Citation | Han X, et al. (2021) PPARalpha agonist exerts protective effects in podocyte injury via inhibition of the ANGPTL3 pathway. Exp Cell Res 407(2):112753 |
| abstractText | Peroxisome proliferator-activated receptor alpha (PPARalpha) activation has been reported to exert protective effects on podocytes, whereas angiopoietin-like 3 (ANGPTL3) has been shown to exert significant pathogenic effects on these cells. This study aimed to investigate the link between the protective effects of PPARalpha activation and the pathogenic effects of ANGPTL3 in podocytes. Both PPARalpha and ANGPTL3 were expressed in cultured podocytes. PPARalpha mRNA and protein levels decreased whereas ANGPTL3 mRNA and protein levels increased in a time-dependent manner in podocytes treated with puromycin aminonucleoside (PAN). Gemfibrozil, a pharmacological agonist of PPARalpha, increased PPARalpha levels and activity in podocytes. The drug also decreased ANGPTL3 levels by potentially weakening ANGPTL3 promoter activity in both normal and PAN-treated podocytes. Furthermore, gemfibrozil significantly decreased PAN-induced apoptosis and F-actin rearrangement. Primary podocytes from Angptl3-knockout mice were cultured. There was no significant difference between Angptl3(-/-) podocytes treated with or without gemfibrozil in the lamellipodia numbers after PAN treatment. The results suggested that the protective effects of gemfibrozil on podocytes were not exerted following knockout of the Angptl3 gene. This study identified a novel mechanism of the PPARalpha agonist gemfibrozil that exerts its protective effects by inhibiting PAN-induced apoptosis and cytoskeleton rearrangements through inhibition of ANGPTL3 expression. |
