title: Impact of heparanase on renal fibrosis.
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.
authors.affiliation: Renal Unit, Department of Medicine, Verona University Hospital, Piazzale A. Stefani 1, 37126, Verona, VR, Italy. valentina.masola@unipd.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Masola
authors.affiliation: Renal Unit, Department of Medicine, Verona University Hospital, Piazzale A. Stefani 1, 37126, Verona, VR, Italy. gianluigi.zaza@univr.it.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Zaza
authors.affiliation: Department of Biomedical Sciences, University of Padova, Padua, Italy. maurizio.onisto@unipd.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Onisto
authors.affiliation: Renal Unit, Department of Medicine, Verona University Hospital, Piazzale A. Stefani 1, 37126, Verona, VR, Italy. antonio.lupo@univr.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lupo
authors.affiliation: Division of Nephrology and Dialysis, Columbus-Gemelli Hospital Catholic University School of Medicine, Rome, Italy. giovanni.gambaro@rm.unicatt.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Gambaro
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005355:Fibrosis; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000201:enzymology* / Q000473:pathology*; D058990:Molecular Targeted Therapy; D000099175:Heparanase
chemical_list: D015415:Biomarkers; D005966:Glucuronidase; D000099175:Heparanase