Impact of heparanase on renal fibrosisReportar como inadecuado




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Journal of Translational Medicine

, 13:181

Nutrition and metabolism

Abstract

Tubulo-interstitial fibrosis has been recognized as the hallmark of progression of chronic kidney disease, but, despite intensive research studies, there are currently no biomarkers or effective treatments for this condition. In this context, a promising candidate could be heparanase-1 HPSE, an endoglycosidase that cleaves heparan sulfate chains and thus takes part in extracellular matrix remodeling. As largely described, it has a central role in the pathogenesis of cancer and inflammation, and it participates in the complex biological machinery involved in the onset of different renal proteinuric diseases e.g., diabetic nephropathy, glomerulonephritis. Additionally, HPSE may significantly influence the progression of chronic kidney damage trough its major role in the biological pathway of renal fibrogenesis. Here, we briefly summarize data supporting the role of HPSE in renal damage, focusing on recent evidences that demonstrate the capability of this enzyme to modulate the signaling of pro-fibrotic factors such as FGF-2 and TGF-β and consequently to control the epithelial-mesenchymal transition in renal tubular cells. We also emphasize the need of the research community to undertake studies and clinical trials to assess the potential clinical employment of this enzyme as diagnostic and prognostic tool and-or its role as therapeutic target for new pharmacological interventions.

AbbreviationsAGEadvanced glycosylation end products

CKDchronic kidney disease

DNdiabetic nephropathy

ESRDend-stage renal disease

EGFepidermal growth factor

EMTepithelial-mesenchymal transdifferentiation

ECMextracellular matrix

FGF-2fibroblast growth factor-2

HPSEheparanase-1

HSheparan sulfate

HSPGsHS-proteoglycans

PBMCperipheral blood mononuclear cell

SDC1syndecan-1

TNF-αtissue necrosis factor-α

TLRstoll-like receptors

TGF-βtransforming growth factor-β

TIFtubulo-interstitial fibrosis

VEGFvascular endothelial growth factor

Valentina Masola and Gianluigi Zaza equally contributed to prepare and to write the present review

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Autor: Valentina Masola - Gianluigi Zaza - Maurizio Onisto - Antonio Lupo - Giovanni Gambaro

Fuente: https://link.springer.com/



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