Tranilast attenuates connective tissue growth factor-induced extracellular matrix accumulation in renal cells

Tranilast (N-[3,4-dimethoxycinnamoyl]anthranilic acid) is a synthetic compound that we have recently reported to inhibit transforming growth factor-β1 (TGF-β1)-induced tubulointerstitial fibrosis in the kidney. Connective tissue growth factor (CTGF) is recognized as a potent downstream mediator of T...

Full description

Saved in:

Bibliographic Details
Published in:	Kidney international Vol. 69; no. 6; pp. 989 - 995
Main Authors:	Qi, W., Chen, X., Twigg, S., Polhill, T.S., Gilbert, R.E., Pollock, C.A.
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Inc 01-03-2006 Nature Publishing Elsevier Limited
Subjects:	Anti-Allergic Agents - pharmacology Biological and medical sciences Blotting, Western Cell Survival Cells, Cultured Collagen Type IV - analysis Collagen Type IV - metabolism Connective Tissue Growth Factor cortical fibroblasts CTGF ECM Extracellular Matrix - chemistry Extracellular Matrix - drug effects Extracellular Matrix - metabolism Fibroblasts - drug effects Fibroblasts - metabolism Fibroblasts - pathology Fibronectins - analysis Fibronectins - metabolism Fibrosis Gene Expression Regulation - drug effects Humans Hypertrophy - pathology Immediate-Early Proteins - genetics Immediate-Early Proteins - physiology Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - physiology Kidney Cortex - drug effects Kidney Cortex - metabolism Kidney Cortex - pathology Kidney Tubules, Proximal - drug effects Kidney Tubules, Proximal - metabolism Kidney Tubules, Proximal - pathology Medical sciences Nephrology. Urinary tract diseases ortho-Aminobenzoates - pharmacology Phosphorylation proximal tubular cells pSmad2 Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - analysis Signal Transduction - physiology Smad2 Protein - analysis Smad2 Protein - physiology TGF-β1 Transforming Growth Factor beta - pharmacology Transforming Growth Factor beta - physiology Transforming Growth Factor beta1 TGF-β1 proximal tubular cells pSmad2 ECM cortical fibroblasts CTGF Proximal Nephrology Connective tissue growth factor Antihistaminic Accumulation Kidney Urology Tranilast Renal tubule Urinary system Extracellular matrix Antagonist Transforming growth factor β1 H1 Histamine receptor Fibroblast
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Tranilast (N-[3,4-dimethoxycinnamoyl]anthranilic acid) is a synthetic compound that we have recently reported to inhibit transforming growth factor-β1 (TGF-β1)-induced tubulointerstitial fibrosis in the kidney. Connective tissue growth factor (CTGF) is recognized as a potent downstream mediator of TGF-β1. Both proximal tubule cells (PTCs) and cortical fibroblasts (CFs) are considered to be responsible for the production of tubulointerstitial extracellular matrix (ECM). These studies were undertaken to assess the profibrotic effects of CTGF in an in vitro model of the human PTCs and CFs, and to determine whether tranilast is effective in limiting the in vitro matrix responses induced by CTGF. Primary cultures of PTCs and CFs were exposed to CTGF (20 ng/ml)±tranilast (100 μM). Cell hypertrophy and the secretion of the ECM proteins fibronectin and collagen IV were determined. The effects of tranilast on TGF-β1-induced CTGF mRNA expression and on phosphorylation of Smad2 were determined. CTGF significantly induced cell hypertrophy, increased fibronectin, and collagen IV secretion in PTCs and CFs. In all cases, the CTGF-induced increase in ECM protein was inhibited in the presence of tranilast. Tranilast reduced CTGF mRNA and phosphorylation of Smad2, which were induced by TGF-β1 in PTCs and CFs. These results suggest that tranilast is a potential effective antifibrotic compound in the kidney, exerting its effects via inhibition of TGF-β1-induced CTGF expression and downstream activation of the Smad2 pathway in both PTCs and CFs.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0085-2538 1523-1755
DOI:	10.1038/sj.ki.5000189