2008
DOI: 10.1038/sj.ki.5002717
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Oral administration of GW788388, an inhibitor of TGF-β type I and II receptor kinases, decreases renal fibrosis

Abstract: Progressive kidney fibrosis precedes end-stage renal failure in up to a third of patients with diabetes mellitus. Elevated intra-renal transforming growth factor-beta (TGF-beta) is thought to underlie disease progression by promoting deposition of extracellular matrix and epithelial-mesenchymal transition. GW788388 is a new TGF-beta type I receptor inhibitor with a much improved pharmacokinetic profile compared with SB431542. We studied its effect in vitro and found that it inhibited both the TGF-beta type I a… Show more

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Cited by 188 publications
(132 citation statements)
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“…Cells were stimulated with TGF-b3 and BMP-6 at 5 and 100 ng/ml, respectively. SB431542 (Tocris bioscience, Bristol, UK) was used at 10 mM as previously reported (Petersen et al, 2008).…”
Section: Methodsmentioning
confidence: 99%
“…Cells were stimulated with TGF-b3 and BMP-6 at 5 and 100 ng/ml, respectively. SB431542 (Tocris bioscience, Bristol, UK) was used at 10 mM as previously reported (Petersen et al, 2008).…”
Section: Methodsmentioning
confidence: 99%
“…Elevated SMAD1 levels are associated with early renal dysfunction and SMAD1 levels in glomeruli are correlated with progression of renal disease [4]. In a mouse model of diabetic nephropathy, inhibition of the TGFβ-SMAD2/3 pathway resulted in reduced renal fibrosis [5]. In a small family-based study, two single nucleotide polymorphisms (SNPs) in SMAD3 were associated with diabetic nephropathy [6].…”
Section: Introductionmentioning
confidence: 99%
“…In addition to physical forces, an alternative mechanism for proteinuria could be attributable to humoral factors that are induced during the disease. For example, inflammatory cytokines or fibrogenic mediators had been shown to modulate podocyte motility and albumin permeability, mRNA expression of podocyte markers such as nephrin and ezrin as well as podocyte survival and adhesion (9)(10)(11)(12)(13)(14)(15). Presumably, through mesangial cellpodocyte communication (16)(17)(18), these effects might lead to breakdown of the glomerular permeability with resultant formation of proteinuria.…”
Section: Discussionmentioning
confidence: 99%
“…Apart from its profibrotic action, TGF-β1 induces podocyte dedifferentiation and causes albumin influx across the podocyte monolayer (11,12). In TGF-β1 transgenic mice, podocytes undergo apoptosis in association with depletion of podocytes early during progressive glomerulosclerosis (32).…”
Section: Discussionmentioning
confidence: 99%
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