| First Author | Lin Q | Year | 2022 |
| Journal | Biochim Biophys Acta Mol Basis Dis | Volume | 1868 |
| Issue | 8 | Pages | 166414 |
| PubMed ID | 35447340 | Mgi Jnum | J:324994 |
| Mgi Id | MGI:7283763 | Doi | 10.1016/j.bbadis.2022.166414 |
| Citation | Lin Q, et al. (2022) FGF1(DeltaHBS) delays the progression of diabetic nephropathy in late-stage type 2 diabetes mouse model by alleviating renal inflammation, fibrosis, and apoptosis. Biochim Biophys Acta Mol Basis Dis 1868(8):166414 |
| abstractText | Elderly adults are at higher risk for developing diabetic complications including diabetic nephropathy (DN), contributing to excess morbidity and mortality in elderly individuals. A non-mitogenic variant of fibroblast growth factor 1 (FGF1(DeltaHBS)) was demonstrated to prevent DN in an early-stage (2-month-old) type 2 diabetes (T2D) mouse model. The present study aimed to investigate the potential therapeutic effects of FGF1(DeltaHBS) against the progression of renal dysfunction in a late-stage T2D mouse model with established DN. Nine-month-old db/db mice were administered FGF1(DeltaHBS) every other day for 3 months. db/db mice at 12-month-old without FGF1(DeltaHBS) treatment exhibited high blood glucose level and elevated urine albumin-to-creatinine ratio. FGF1(DeltaHBS) treatment effectively reversed hyperglycemia, delayed the development of renal dysfunction, and reduced kidney size and weight. Furthermore, FGF1(DeltaHBS) treatment significantly prevented the progression of renal morphologic impairment. FGF1(DeltaHBS) treatment demonstrated anti-inflammatory and anti-fibrotic effects, with significantly decreased protein levels of key pro-inflammatory cytokines and pro-fibrotic factors in kidney. Moreover, FGF1(DeltaHBS) treatment greatly decreased apoptosis of renal tubular cells, accompanied by significant downregulation of the proapoptotic protein and upregulation of the antiapoptotic protein and peroxisome proliferator-activated receptor alpha (PPARalpha) expression in kidney. Mechanistically, FGF1(DeltaHBS) treatment directly protected mouse proximal tubule cells against palmitate-induced apoptosis, which was abolished by PPARalpha inhibition. In conclusion, this study demonstrated that FGF1(DeltaHBS) delays the progression of renal dysfunction likely through activating PPARalpha to prevent renal tubule cell death in late-stage T2D, exhibiting a promising translational potential in treating DN in elderly T2D individuals by ameliorating renal inflammation, fibrosis and apoptosis. |
