Targeting CTGF, EGF and PDGF Pathways to Prevent Progression of Kidney Disease

Overview

Journal Nat Rev Nephrol

Specialty Nephrology

Date 2014 Oct 15

PMID 25311535

Citations 73

Authors

Helena M Kok

Lucas L Falke

Roel Goldschmeding

Tri Q Nguyen

Affiliations

Soon will be listed here.

Abstract

Chronic kidney disease (CKD) is a major health and economic burden with a rising incidence. During progression of CKD, the sustained release of proinflammatory and profibrotic cytokines and growth factors leads to an excessive accumulation of extracellular matrix. Transforming growth factor β (TGF-β) and angiotensin II are considered to be the two main driving forces in fibrotic development. Blockade of the renin-angiotensin-aldosterone system has become the mainstay therapy for preservation of kidney function, but this treatment is not sufficient to prevent progression of fibrosis and CKD. Several factors that induce fibrosis have been identified, not only by TGF-β-dependent mechanisms, but also by TGF-β-independent mechanisms. Among these factors are the (partially) TGF-β-independent profibrotic pathways involving connective tissue growth factor, epidermal growth factor and platelet-derived growth factor and their receptors. In this Review, we discuss the specific roles of these pathways, their interactions and preclinical evidence supporting their qualification as additional targets for novel antifibrotic therapies.

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