title: Human mesangial cells resist glycoxidative stress through an antioxidant response.
abstract: The generation of advanced glycation end-products (AGE), the interaction with their receptors, the generation of reactive oxygen species, and the modulation of intracellular redox equilibrium are believed to be the main factors causing alterations of mesangial cell physiology leading to diabetic nephropathy. Normal human primary mesangial cells were exposed to glycoxidative stress by culture in high glucose (HG) or treatment with AGE for up to 6 days. In both cases only a moderate generation of reactive oxygen species and production of HNE-protein adducts were induced while protein nitrotyrosination was not affected. Moreover, HG and AGE caused a significant antioxidant response, confirmed by the induction of heme oxygenase 1 and the consumption of vitamin E. Glutathione was decreased only by HG. Mesangial cell proliferation and viability were slightly affected by HG and AGE. Furthermore, both treatments failed to influence TGF-ß1 and MCP-1 secretion and to modulate RAGE and collagen IV expression. We believe that normal human mesangial cells can resist glycoxidative stress by the observed antioxidant response. These results support the concept that mesangial cells are only partly responsible for the onset and progression of diabetic nephropathy and that the role of other cell types, such as podocytes and endothelial cells, should be taken into consideration.
authors.affiliation: Department of Experimental Medicine, University of Genoa, Genoa, Italy.
authors.forename: Mariapaola
authors.initials: M
authors.lastname: Nitti
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Furfaro
authors.forename: Stefania
authors.initials: S
authors.lastname: Patriarca
authors.forename: Emanuela
authors.initials: E
authors.lastname: Balbis
authors.forename: Cinzia
authors.initials: C
authors.lastname: Domenicotti
authors.forename: Damiano
authors.initials: D
authors.lastname: Cottalasso
authors.forename: Maria Adelaide
authors.initials: MA
authors.lastname: Pronzato
authors.forename: Umberto Maria
authors.initials: UM
authors.lastname: Marinari
authors.forename: Nicola
authors.initials: N
authors.lastname: Traverso
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050527:Mesangial Cells / Q000187:drug effects / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D018932:Chemokine CCL2; D017127:Glycation End Products, Advanced; D016877:Oxidants; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D053773:Transforming Growth Factor beta1; D003094:Collagen; D006861:Hydrogen Peroxide; D005947:Glucose