Journal article

Advanced glycation end products activate Smad signaling via TGF-beta-dependent and -independent mechanisms: implications for diabetic renal and vascular disease

JH Li, XR Huang, HJ Zhu, M Oldfield, M Cooper, LD Truong, RJ Johnson, HY Lan

FASEB JOURNAL | FEDERATION AMER SOC EXP BIOL | Published : 2004

Abstract

While it is thought that advanced glycation end products (AGEs) act by stimulating transforming growth factor (TGF)-beta to mediate diabetic injury, we report that AGEs can activate TGF-beta signaling, Smads, and mediate diabetic scarring directly and independently of TGF-beta. AGEs activate Smad2/3 in renal and vascular cells at 5 min, peaking over 15-30 min before TGF-beta synthesis at 24 h and occurs in TGF-beta receptor I and II mutant cells. This is mediated by RAGE and ERK/p38 mitogen-activated protein kinases (MAPKs). In addition, AGEs also activate Smads at 24 h via the classic TGF-beta-dependent pathway. A substantial inhibition of AGE-induced Smad activation and collagen synthesis ..

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