| First Author | Li L | Year | 2021 |
| Journal | EMBO Rep | Volume | 22 |
| Issue | 6 | Pages | e51169 |
| PubMed ID | 34031962 | Mgi Jnum | J:307063 |
| Mgi Id | MGI:6712130 | Doi | 10.15252/embr.202051169 |
| Citation | Li L, et al. (2021) Orphan nuclear receptor COUP-TFII enhances myofibroblast glycolysis leading to kidney fibrosis. EMBO Rep :e51169 |
| abstractText | Recent studies demonstrate that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP-TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP-TFII in mice resulted in attenuation of injury-induced kidney fibrosis. A non-biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP-TFII overexpressing fibroblasts. Overexpression of COUP-TFII in fibroblasts also induced production of alpha-smooth muscle actin (alphaSMA) and collagen 1. Knockout of COUP-TFII decreased glycolysis and collagen 1 levels in fibroblasts. Chip-qPCR revealed the binding of COUP-TFII on the promoter of PGC1alpha. Overexpression of COUP-TFII reduced the cellular level of PGC1alpha. Targeting COUP-TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs. |
