| First Author | Escasany E | Year | 2021 |
| Journal | Dis Model Mech | Volume | 14 |
| Issue | 9 | PubMed ID | 34431499 |
| Mgi Jnum | J:311746 | Mgi Id | MGI:6780671 |
| Doi | 10.1242/dmm.048249 | Citation | Escasany E, et al. (2021) Transforming growth factor beta3 deficiency promotes defective lipid metabolism and fibrosis in murine kidney. Dis Model Mech 14(9):dmm048249 |
| abstractText | Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor beta (TGFbeta) is a key player in the development of fibrosis. However, of the three known TGFbeta isoforms, only TGFbeta1 has an established role in fibrosis, and the pathophysiological relevance of TGFbeta2 and TGFbeta3 is unknown. Because Tgfb3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfb3-knockout mice (Tgfb3+/-) and compared it with that of matched wild-type mice. Four-month-old Tgfb3+/- mice exhibited incipient renal fibrosis with epithelial-mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level, together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis revealed toxic species, such as diacylglycerides and ceramides, and dysregulated mitochondrial metabolism in Tgfb3+/- mice. Kidneys of Tgfb3+/- mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study indicates that renal TGFbeta3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGFbeta1. This article has an associated First Person interview with the first author of the paper. |
