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: TGF-[beta]1 binds receptor II (T[beta]RII) to exert its biological activities but its functional importance in kidney diseases remains largely unclear. In the present study, we hypothesized that T[beta]RII may function to initiate the downstream TGF-[beta] signalling and determine the diverse role of TGF-[beta]1 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 T[beta]RII was deleted conditionally. We found that disruption of T[beta]RII 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 T[beta]RII enhanced NF-[kappa]B signalling and renal inflammation including up-regulation of Il-1[beta] and Tnf[alpha] in the UUO kidney. Similarly, in vitro disruption of T[beta]RII from kidney fibroblasts or tubular epithelial cells inhibited TGF-[beta]1-induced Smad signalling and fibrosis but impaired the anti-inflammatory effect of TGF-[beta]1 on IL-1[beta]-stimulated NF-[kappa]B activation and pro-inflammatory cytokine expression. In conclusion, T[beta]RII 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 T[beta]RII protects against renal fibrosis. In addition, deletion of T[beta]RII also enhances NF-[kappa]B signalling along with up-regulation of renal pro-inflammatory cytokines, which may be associated with the impairment of anti-inflammatory properties of TGF-[beta]1. Copyright (C) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Copyright (C) 2012 John Wiley & Sons, Inc.