Chor Ho Jo, Sua Kim, Tae Kyung Ha, Duk-Hee Kang, Gheun-Ho Kim
{"title":"Effects of sitagliptin on peritoneal membrane: The potential role of mesothelial cell tight junction proteins.","authors":"Chor Ho Jo, Sua Kim, Tae Kyung Ha, Duk-Hee Kang, Gheun-Ho Kim","doi":"10.1177/08968608231158224","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The roles of tight junction (TJ) proteins in peritoneal membrane transport and peritoneal dialysis (PD) require further characterisation. Dipeptidyl peptidase-4 is expressed in mesothelial cells, and its activity may affect peritoneal membrane function and morphology.</p><p><strong>Methods: </strong>Human peritoneal mesothelial cells (HPMCs) were isolated and cultured from omentum obtained during abdominal surgery, and paracellular transport functions were evaluated by measuring transmesothelial electrical resistance (TMER) and dextran flux. Sprague-Dawley rats were infused daily with 4.25% peritoneal dialysate with and without sitagliptin administration for 8 weeks. At the end of this period, rat peritoneal mesothelial cells (RPMCs) were isolated to evaluate TJ protein expression.</p><p><strong>Results: </strong>In HPMCs, the protein expression of claudin-1, claudin-15, occludin and E-cadherin was decreased by TGF-β treatment but reversed by sitagliptin co-treatment. TMER was decreased by TGF-β treatment but improved by sitagliptin co-treatment. Consistent with this, dextran flux was increased by TGF-β treatment and reversed by sitagliptin co-treatment. In the animal experiment, sitagliptin-treated rats had a lower D2/D0 glucose ratio and a higher D2/P2 creatinine ratio than PD controls during the peritoneal equilibration test. Protein expression of claudin-1, claudin-15 and E-cadherin decreased in RPMCs from PD controls but was not affected in those from sitagliptin-treated rats. Peritoneal fibrosis was induced in PD controls but ameliorated in sitagliptin-treated rats.</p><p><strong>Conclusion: </strong>The expression of TJ proteins including claudin-1 and claudin-15 was associated with transport function both in HPMCs and in a rat model of PD. Sitagliptin prevents peritoneal fibrosis in PD and can potentially restore peritoneal mesothelial cell TJ proteins.</p>","PeriodicalId":19969,"journal":{"name":"Peritoneal Dialysis International","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Peritoneal Dialysis International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/08968608231158224","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/3/30 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"UROLOGY & NEPHROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: The roles of tight junction (TJ) proteins in peritoneal membrane transport and peritoneal dialysis (PD) require further characterisation. Dipeptidyl peptidase-4 is expressed in mesothelial cells, and its activity may affect peritoneal membrane function and morphology.
Methods: Human peritoneal mesothelial cells (HPMCs) were isolated and cultured from omentum obtained during abdominal surgery, and paracellular transport functions were evaluated by measuring transmesothelial electrical resistance (TMER) and dextran flux. Sprague-Dawley rats were infused daily with 4.25% peritoneal dialysate with and without sitagliptin administration for 8 weeks. At the end of this period, rat peritoneal mesothelial cells (RPMCs) were isolated to evaluate TJ protein expression.
Results: In HPMCs, the protein expression of claudin-1, claudin-15, occludin and E-cadherin was decreased by TGF-β treatment but reversed by sitagliptin co-treatment. TMER was decreased by TGF-β treatment but improved by sitagliptin co-treatment. Consistent with this, dextran flux was increased by TGF-β treatment and reversed by sitagliptin co-treatment. In the animal experiment, sitagliptin-treated rats had a lower D2/D0 glucose ratio and a higher D2/P2 creatinine ratio than PD controls during the peritoneal equilibration test. Protein expression of claudin-1, claudin-15 and E-cadherin decreased in RPMCs from PD controls but was not affected in those from sitagliptin-treated rats. Peritoneal fibrosis was induced in PD controls but ameliorated in sitagliptin-treated rats.
Conclusion: The expression of TJ proteins including claudin-1 and claudin-15 was associated with transport function both in HPMCs and in a rat model of PD. Sitagliptin prevents peritoneal fibrosis in PD and can potentially restore peritoneal mesothelial cell TJ proteins.
期刊介绍:
Peritoneal Dialysis International (PDI) is an international publication dedicated to peritoneal dialysis. PDI welcomes original contributions dealing with all aspects of peritoneal dialysis from scientists working in the peritoneal dialysis field around the world.
Peritoneal Dialysis International is included in Index Medicus and indexed in Current Contents/Clinical Practice, the Science Citation Index, and Excerpta Medica (Nephrology/Urology Core Journal). It is also abstracted and indexed in Chemical Abstracts (CA), as well as being indexed in Embase as a priority journal.