Glycated adducts induce mesothelial cell transdifferentiation: role of glucose and icodextrin dialysis solutions. 2008

Giovanni Conti, and Alessandro Amore, and Paola Cirina, and Licia Peruzzi, and Sabrina Balegno, and Rosanna Coppo
Nephrology, Dialysis and Transplantation Unit, Regina Margherita Hospital, Turin, Italy.

BACKGROUND In peritoneal dialysis (PD), the peritoneum is exposed to intermediate Amadori adducts (AmAs) and advanced (AGE) glycated products of proteins. The aim of this study was to test the capacity of AmAs created in different PD solutions (PDSs) to elicit a fibroblast-like transdifferentiation of human peritoneal mesothelial cells (HPMCs) in culture. METHODS HPMCs were incubated for 12 hours with AmA obtained by human serum albumin (HSA) incubated for 6 days with commercial 3.86% glucose (Glu), 1.36% Glu and 7.5% icodextrin (Ico) PDS. Mesenchymal (vimentin), epithelial (cadherin) and myofibroblastic (Type I collagen and alpha smooth muscle cell actin [ASMA]) markers were evaluated (RT-PCR, immunostaining and Western blot), as well as TGF-b3 synthesis (ELISA and Western blot). RESULTS Ico-PDS was less active than 3.86% and 1.36% Glu-PDS in glycating albumin (p<0.001). AmA-HSA-Glu 3.86% and 1.36% induced a significantly higher increase in vimentin and Type I collagen mRNA expression than AmA-HSA-Ico (p<0.0001). By contrast, AmA-HSA-Glu 3.86% and 1.36% induced a reduction in cadherin mRNA expression which was significantly different from AmA- HSA-Ico (p<0.0001). RT-PCR data were confirmed by immunostaining and Western blot analysis. AmA-HSA-Glu 3.86% and 1.36% induced a significantly higher increase in ASMA mRNA expression than AmA-HSA-Ico (p<0.0001). AmA-HSA-Glu 3.86% and 1.36% stimulated ASMA and TGF-b3 synthesis which were significantly higher than AmA-HSA-Ico (p<0.001 and p<0.01, respectively). CONCLUSIONS Our data suggest that Glu-PDS, but not Ico-PDS, can turn on the fibroblastic-like transdifferentiation in HPMCs, and this mechanism may result in peritoneal sclerosis.

UI MeSH Term Description Entries
D010530 Peritoneal Dialysis Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure. Dialyses, Peritoneal,Dialysis, Peritoneal,Peritoneal Dialyses
D010537 Peritoneum A membrane of squamous EPITHELIAL CELLS, the mesothelial cells, covered by apical MICROVILLI that allow rapid absorption of fluid and particles in the PERITONEAL CAVITY. The peritoneum is divided into parietal and visceral components. The parietal peritoneum covers the inside of the ABDOMINAL WALL. The visceral peritoneum covers the intraperitoneal organs. The double-layered peritoneum forms the MESENTERY that suspends these organs from the abdominal wall. Parietal Peritoneum,Peritoneum, Parietal,Peritoneum, Visceral,Visceral Peritoneum,Parametrium,Parametriums
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005936 Glucans Polysaccharides composed of repeating glucose units. They can consist of branched or unbranched chains in any linkages. Glucan,Polyglucose,Polyglucoses,Glucan (BO),Glucose Polymer,Polycose,Polymer, Glucose
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077607 Icodextrin A glucan that is structurally related to maltodextrin, with more than 85% of its molecules having molecular weights between 1640 and 45 000 Daltons (Da), and a weight-average molecular weight of about 20 000 Da; it is used in dialysis fluids as an alternative to glucose-based solutions, and to reduce adhesions after gynecological or abdominal surgery. It has also been used as a vehicle for drugs given via the peritoneal cavity. Extraneal,Icodial
D000093423 Glycated Serum Albumin Serum albumin that has undergone, in vivo, spontaneous, non-enzymatic modification with reducing sugars via the MAILLARD REACTION. They are analyzed to measure control of HYPERGLYCEMIA. Glycated Albumin, Serum,Glycoalbumin,Glycosyl-Albumin,Glycosylated Serum Albumin,Serum Albumin, Glycosylated,Albumin, Glycated Serum,Albumin, Glycosylated Serum,Albumin, Serum Glycated,Glycosyl Albumin,Serum Albumin, Glycated,Serum Glycated Albumin

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