Progression of Tubulointerstitial Fibrosis and the Chronic Kidney Disease Phenotype - Role of Risk Factors and Epigenetics

Although the kidney has capacity to repair after mild injury, ongoing or severe damage results in scarring (fibrosis) and an associated progressive loss of kidney function. However, despite its universal significance, evidence highlights a population based heterogeneity in the trajectory of chronic...

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Published inFrontiers in pharmacology Vol. 8; p. 520
Main Authors Hewitson, Timothy D, Holt, Stephen G, Smith, Edward R
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Media S.A 08.08.2017
Subjects
autocrine
epigenetics
fibrogenesis
fibrosis
kidney disease
Pharmacology
TGF-β1
TGF-β1
kidney disease
fibrosis
fibrogenesis
autocrine
epigenetics
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Summary:Although the kidney has capacity to repair after mild injury, ongoing or severe damage results in scarring (fibrosis) and an associated progressive loss of kidney function. However, despite its universal significance, evidence highlights a population based heterogeneity in the trajectory of chronic kidney disease (CKD) in these patients. To explain the heterogeneity of the CKD phenotype requires an understanding of the relevant risk factors for fibrosis. These factors include both the extrinsic nature of injury, and intrinsic factors such as age, gender, genetics, and perpetual activation of fibroblasts through priming. In many cases an additional level of regulation is provided by epigenetic mechanisms which integrate the various pro-fibrotic and anti-fibrotic triggers in fibrogenesis. In this review we therefore examine the various molecular and structural changes of fibrosis, and how they are influenced by extrinsic and intrinsic factors. Our aim is to provide a unifying hypothesis to help explain the transition from acute to CKD.
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This article was submitted to Cardiovascular and Smooth Muscle Pharmacology, a section of the journal Frontiers in Pharmacology
Edited by: Issy Laher, University of British Columbia, Canada
Reviewed by: Nazareno Paolocci, Johns Hopkins University, United States; Gaetano Santulli, Columbia University, United States; Bisher Hassan Abuyassin, University of British Columbia, Canada
ISSN:1663-9812
1663-9812
DOI:10.3389/fphar.2017.00520