Connective tissue growth factor(CCN2), a pathogenic factor in diabetic nephropathy. What does it do? How does it do it?
Open Access
- 14 February 2009
- journal article
- review article
- Published by Wiley in Journal of Cell Communication and Signaling
- Vol. 3 (2), 95-104
- https://doi.org/10.1007/s12079-009-0038-6
Abstract
Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of matricellular proteins. Its expression is induced by a number of factors including TGF-β. It has been associated with fibrosis in various tissues including the kidney. Diabetic nephropathy (DN) develops in about 30% of patients with diabetes and is characterized by thickening of renal basement membranes, fibrosis in the glomerulus (glomerulosclerosis), tubular atrophy and interstitial fibrosis, all of which compromise kidney function. This review examines changes in CTGF expression in the kidney in DN, the effects they have on glomerular mesangial and podocyte cells and the tubulointerstitium, and how these contribute to driving fibrotic changes in the disease. CTGF can bind to several other growth factors modifying their function. CTGF is also able to interact with receptors on cells, including integrins, tyrosine receptor kinase A (TrkA), low density lipoprotein receptor-related protein (LRP) and heparan sulphate proteoglycans. These interactions, the intracellular signalling pathways they activate, and the cellular responses evoked are reviewed. CTGF also induces the expression of chemokines which themselves have pharmacological actions on cells. CTGF may prompt some responses by acting through several different mechanisms, possibly simultaneously. For example, CTGF is often described as an effector of TGF-β. It can promote TGF-β signalling by binding directly to the growth factor, promoting its interaction with the TGF-β receptor; by triggering intracellular signalling on binding the TrkA receptor, which leads to the transcriptional repression of Smad7, an inhibitor of the TGF-β signalling pathway; and by binding to BMP-7 whose own signalling pathway opposing TGF-β is inhibited, leading to enhanced TGF-β signalling.Keywords
Funding Information
- Diabetes UK
This publication has 89 references indexed in Scilit:
- Pericytes and Perivascular Fibroblasts Are the Primary Source of Collagen-Producing Cells in Obstructive Fibrosis of the KidneyThe American Journal of Pathology, 2008
- Fibroblasts in Kidney Fibrosis Emerge via Endothelial-to-Mesenchymal TransitionJournal of the American Society of Nephrology, 2008
- CTGF Inhibits BMP-7 Signaling in Diabetic NephropathyJournal of the American Society of Nephrology, 2008
- Nerve Growth Factor Stimulates the Concentration of TrkA within Lipid Rafts and Extracellular Signal-Regulated Kinase Activation through c-Cbl-Associated ProteinMolecular and Cellular Biology, 2007
- Podocyte biology in diabetic nephropathyKidney International, 2007
- Connective tissue growth factor (CTGF) promotes activated mesangial cell survival via up-regulation of mitogen-activated protein kinase phosphatase-1 (MKP-1)Biochemical Journal, 2007
- Histopathology of Diabetic NephropathySeminars in Nephrology, 2007
- Heparan Sulfate Analysis from Diabetic Rat GlomeruliOnline Journal of Public Health Informatics, 2007
- BMP7 signaling in renal development and diseaseTrends in Molecular Medicine, 2005
- Morphometric studies of the peripheral glomerular basement membrane in early juvenile diabetes I. Development of initial basement membrane thickeningDiabetologia, 1972