title: [High glucose dialysate enhances peritoneal fibrosis through upregulating glucose transporters GLUT1 and SGLT1].
abstract: Objective:To investigate the role of glucose transporter 1 (GLUT1) and sodium-glucose cotransporter 1 (SGLT1) in high glucose dialysate-induced peritoneal fibrosis.Methods:Thirty six male SD rats were randomly divided into 6 groups (6 in each):normal control group, sham operation group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorizin group (PD+Z group), PD+phloretin+phlorizin group (PD+T+Z group). Rat model of uraemia was established using 5/6 nephrotomy, and 2.5% dextrose peritoneal dialysis solution was used in peritoneal dialysis. Peritoneal equilibration test was performed 24 h after dialysis to evaluate transport function of peritoneum in rats; HE staining was used to observe the morphology of peritoneal tissue; and immunohistochemistry was used to detect the expression of GLUT1, SGLT1, TGF-β1 and connective tissue growth factor (CTGF) in peritoneum. Human peritoneal microvascular endothelial cells (HPECs) were divided into 5 groups:normal control group, peritoneal dialysis group (PD group), PD+phloretin group (PD+T group), PD+phlorezin group (PD+Z group), and PD+phloretin+phlorezin group (PD+T+Z group). Real time PCR and Western blotting were used to detect mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF in peritoneal membrane and HPECs.Results:In vivo, compared with sham operation group, rats in PD group had thickened peritoneum, higher ultrafiltration volume, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly increased (allP<0.05); compared with PD group, thickened peritoneum was attenuated, and the mRNA and protein expressions of GLUT1, SGLT1, CTGF, TGF-β1 were significantly decreased in PD+T, PD+Z and PD+T+Z groups (allP<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in peritoneum were positively correlated with the expressions of TGF-β1 and CTGF (allP<0.05).In vitro, the mRNA and protein expressions of GLUT1, SGLT1, TGF-β1, CTGF were significantly increased in HPECs of peritoneal dialysis group (allP<0.05), and those in PD+T, PD+Z, and PD+T+Z groups were decreased (allP<0.05). Pearson's correlation analysis showed that the expressions of GLUT1, SGLT1 in HPECs were positively correlated with the expressions of TGF-β1 and CTGF (allP<0.05).Conclusion:High glucose peritoneal dialysis fluid may promote peritoneal fibrosis by upregulating the expressions of GLUT1 and SGLT1.
authors.affiliation: School of Medicine, Ningbo University, Ningbo 315211, China.
authors.forename: Mengqi
authors.initials: M
authors.lastname: Hong
authors.affiliation: Division of Nephrology, Ningbo Urology and Nephrology Hospital, School of Medicine, Ningbo University, Ningbo 315192, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Nie
authors.affiliation: Division of Nephrology, Ningbo Urology and Nephrology Hospital, School of Medicine, Ningbo University, Ningbo 315192, China.
authors.forename: Zhengyue
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Division of Nephrology, Ningbo Urology and Nephrology Hospital, School of Medicine, Ningbo University, Ningbo 315192, China.
authors.forename: Xiongwei
authors.initials: X
authors.lastname: Yu
authors.affiliation: Division of Nephrology, Ningbo Urology and Nephrology Hospital, School of Medicine, Ningbo University, Ningbo 315192, China. baobeiyan2007@sina.com.
authors.forename: Beiyan
authors.initials: B
authors.lastname: Bao
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000032:analysis / Q000187:drug effects; D015314:Dialysis Solutions / Q000009:adverse effects* / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000009:adverse effects* / Q000494:pharmacology*; D051272:Glucose Transporter Type 1 / Q000032:analysis / Q000187:drug effects* / Q000502:physiology*; D017583:Hemodiafiltration / Q000009:adverse effects* / Q000379:methods*; D006801:Humans; D008297:Male; D010530:Peritoneal Dialysis / Q000009:adverse effects* / Q000379:methods*; D056627:Peritoneal Fibrosis / Q000139:chemically induced* / Q000235:genetics* / Q000503:physiopathology; D010537:Peritoneum / Q000737:chemistry* / Q000187:drug effects* / Q000473:pathology*; D010693:Phloretin; D010695:Phlorhizin; D012333:RNA, Messenger; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000032:analysis / Q000187:drug effects* / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000187:drug effects; D014511:Uremia / Q000139:chemically induced*
chemical_list: D015314:Dialysis Solutions; D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; D051269:Sodium-Glucose Transporter 1; D053773:Transforming Growth Factor beta1; D055513:Connective Tissue Growth Factor; D010695:Phlorhizin; D005947:Glucose; D010693:Phloretin