title: Targeting CTGF, EGF and PDGF pathways to prevent progression of kidney disease.
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.
authors.affiliation: Department of Pathology, H04.312, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
authors.forename: Helena M
authors.initials: HM
authors.lastname: Kok
authors.affiliation: Department of Pathology, H04.312, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Falke
authors.affiliation: Department of Pathology, H04.312, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
authors.forename: Roel
authors.initials: R
authors.lastname: Goldschmeding
authors.affiliation: Department of Pathology, H04.312, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, Netherlands.
authors.forename: Tri Q
authors.initials: TQ
authors.lastname: Nguyen
mesh_terms: D055513:Connective Tissue Growth Factor / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D066255:EGF Family of Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D051436:Renal Insufficiency, Chronic / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D066255:EGF Family of Proteins; D010982:Platelet-Derived Growth Factor; D055513:Connective Tissue Growth Factor