{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T14:46:02Z","timestamp":1781361962882,"version":"3.54.1"},"reference-count":62,"publisher":"Oxford University Press (OUP)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background. Epithelial-to-mesenchymal transition (EMT) of peritoneal mesothelial cells induced by high glucose (HG) levels is a major biological mechanism leading to myofibroblast accumulation in the omentum of patients on peritoneal dialysis (PD). Heparanase (HPSE), an endoglycosidase that cleaves heparan sulfate chains, is involved in the EMT of several cell lines, and may have a major role in this pro-fibrotic process potentially responsible for the failure of dialysis. Its specific inhibition may therefore plausibly minimize this pathological condition.<\/jats:p>\n                  <jats:p>Methods. An in vitro study employing several biomolecular strategies was conducted to assess the role of HPSE in the HG-induced mesothelial EMT process, and to measure the effects of its specific inhibition by SST0001, a N-acetylated glycol-split heparin with a strong anti-HPSE activity. Rat mesothelial cells were grown for 6 days in HG (200\u2009mM) culture medium with or without SST0001. Then EMT markers (VIM, \u03b1-SMA, TGF-\u03b2) and vascular endothelial growth factor (VEGF) (a factor involved in neoangiogenesis) were measured by real-time PCR and immunofluorescence\/western blotting. As a functional analysis, trans-epithelial resistance (TER) and permeability to albumin were also measured in our in vitro model using a Millicell-ERS ohmmeter and a spectrophotometer, respectively.<\/jats:p>\n                  <jats:p>Results. Our results showed that 200\u2009mM of glucose induced a significant gene and protein up-regulation of VEGF and all EMT markers after 6 days of culture. Intriguingly, adding SST0001 on day 3 reversed these biological and cellular effects. HPSE inhibition also restored the normal TER and permeability lost during the HG treatment.<\/jats:p>\n                  <jats:p>Conclusion. Taken together, our data confirm that HG can induce EMT of mesothelial cells, and that HPSE plays a central part in this process. Our findings also suggest that pharmacological HPSE inhibition could prove a valuable therapeutic tool for minimizing fibrosis and avoiding a rapid decline in the efficacy of dialysis in patients on PD, though clinical studies and\/or trials would be needed to confirm the clinical utility of this treatment.<\/jats:p>","DOI":"10.1093\/ndt\/gfw403","type":"journal-article","created":{"date-parts":[[2016,10,19]],"date-time":"2016-10-19T15:07:54Z","timestamp":1476889674000},"page":"1145-1154","source":"Crossref","is-referenced-by-count":11,"title":["Specific heparanase inhibition reverses glucose-induced mesothelial-to-mesenchymal transition"],"prefix":"10.1093","volume":"32","author":[{"given":"Valentina","family":"Masola","sequence":"first","affiliation":[{"name":"1Renal Unit, Department of Medicine, Verona University Hospital, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Granata","sequence":"additional","affiliation":[{"name":"1Renal Unit, Department of Medicine, Verona University Hospital, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Bellin","sequence":"additional","affiliation":[{"name":"1Renal Unit, Department of Medicine, Verona University Hospital, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Gambaro","sequence":"additional","affiliation":[{"name":"2Nephrology and Dialysis Division, Columbus-Gemelli Hospital, Catholic University School of Medicine, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurizio","family":"Onisto","sequence":"additional","affiliation":[{"name":"3Department of Biomedical Sciences, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Rugiu","sequence":"additional","affiliation":[{"name":"1Renal Unit, Department of Medicine, Verona University Hospital, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Lupo","sequence":"additional","affiliation":[{"name":"1Renal Unit, Department of Medicine, Verona University Hospital, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluigi","family":"Zaza","sequence":"additional","affiliation":[{"name":"1Renal Unit, Department of Medicine, Verona University Hospital, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,1,7]]},"reference":[{"key":"2025102312484342600_gfw403-B1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1186\/s12882-015-0051-3","article-title":"How has peritoneal dialysis changed over the last 30 years: experience of the Verona dialysis center","volume":"16","author":"Zaza","year":"2015","journal-title":"BMC Nephrol"},{"key":"2025102312484342600_gfw403-B2","doi-asserted-by":"crossref","first-page":"S108","DOI":"10.1177\/089686080902902S20","article-title":"Peritoneal dialysis and preservation of residual renal function","volume":"29 (Suppl 2)","author":"Tam","year":"2009","journal-title":"Perit Dial Int"},{"key":"2025102312484342600_gfw403-B3","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1093\/ndt\/gfl601","article-title":"Cardiovascular disease in haemodialysis and peritoneal dialysis: arguments pro peritoneal dialysis","volume":"22","author":"Van Biesen","year":"2007","journal-title":"Nephrol Dial Transplant"},{"key":"2025102312484342600_gfw403-B4","first-page":"132","article-title":"Quality of life in patients undergoing hemodialysis or peritoneal dialysis treatment","volume":"3","author":"Theofilou","year":"2011","journal-title":"J Clin Med Res"},{"key":"2025102312484342600_gfw403-B5","first-page":"S87","article-title":"Studying the effects of new peritoneal dialysis solutions on the peritoneum","volume":"27 (Suppl 2)","author":"Chan","year":"2007","journal-title":"Perit Dial Int"},{"key":"2025102312484342600_gfw403-B6","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1177\/089686080002005S03","article-title":"Effects of conventional and new peritoneal dialysis solutions on human peritoneal mesothelial cell viability and proliferation","volume":"20 (Suppl 5)","author":"Ha","year":"2000","journal-title":"Perit Dial Int"},{"key":"2025102312484342600_gfw403-B7","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1681\/ASN.V132470","article-title":"Peritoneal Biopsy Study Group. 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