| First Author | Meng XM | Year | 2012 |
| Journal | J Pathol | Volume | 227 |
| Issue | 2 | Pages | 175-88 |
| PubMed ID | 22190171 | Mgi Jnum | J:183441 |
| Mgi Id | MGI:5318668 | Doi | 10.1002/path.3976 |
| Citation | Meng XM, et al. (2012) Diverse roles of TGF-beta receptor II in renal fibrosis and inflammation in vivo and in vitro. J Pathol 227(2):175-88 |
| abstractText | TGF-beta1 binds receptor II (TbetaRII) to exert its biological activities but its functional importance in kidney diseases remains largely unclear. In the present study, we hypothesized that TbetaRII may function to initiate the downstream TGF-beta signalling and determine the diverse role of TGF-beta1 in kidney injury. The hypothesis was examined in a model of unilateral ureteral obstructive (UUO) nephropathy and in kidney fibroblasts and tubular epithelial cells in which the TbetaRII was deleted conditionally. We found that disruption of TbetaRII inhibited severe tubulointerstitial fibrosis in the UUO kidney, which was associated with the impairment of TGF-beta/Smad3 signalling, but not with the ERK/p38 MAP kinase pathway. In contrast, deletion of TbetaRII enhanced NF-kappaB signalling and renal inflammation including up-regulation of Il-1beta and Tnfalpha in the UUO kidney. Similarly, in vitro disruption of TbetaRII from kidney fibroblasts or tubular epithelial cells inhibited TGF-beta1-induced Smad signalling and fibrosis but impaired the anti-inflammatory effect of TGF-beta1 on IL-1beta-stimulated NF-kappaB activation and pro-inflammatory cytokine expression. In conclusion, TbetaRII plays an important but diverse role in regulating renal fibrosis and inflammation. Impaired TGF-beta/Smad3, but not the non-canonical TGF-beta signalling pathway, may be a key mechanism by which disruption of TbetaRII protects against renal fibrosis. In addition, deletion of TbetaRII also enhances NF-kappaB signalling along with up-regulation of renal pro-inflammatory cytokines, which may be associated with the impairment of anti-inflammatory properties of TGF-beta1. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
