Acute and chronic exposure to high levels of glucose modulates tight junction-associated epithelial barrier function in a renal tubular cell line

Author(s)

Mongelli-Sabino, B. M. ^[1] ; Canuto, L. P. ^[1] ; Collares-Buzato, C. B. ^[1]

Affiliation

^[1] Univ Estadual Campinas, Inst Biol, Dept Biochem & Tissue Biol, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Life Sciences; v. 188, p. 149-157, NOV 1 2017.
• Web of Science Citations: 4

Abstract

Aims: Type 2 diabetes mellitus (T2DM) is one of the most prevalent diseases worldwide. Diabetic nephropathy (DN) is a complication of diabetes and the mechanisms underlying onset and progression of this disease are not fully understood. It has been shown that hyperglycemia is an independent factor to predict the development of DN in individuals with T2DM, however, a link between high plasma glucose levels and renal tubular injuries in DN remains unknown. In this study, we investigated the effect of high levels of glucose (i.e. 180 or 360 mg/dL) for up to 24 h (acute) or over 72 h (chronic) upon tight junction (TJ)-mediated epithelial barrier integrity of the kidney tubular cell line, MDCK. Methods/key findings: High levels of glucose (180 and 360 mg/dL) induced a decrease in transepithelial electrical resistance associated with an increase in TJ cation selectivity at 24 h or in TJ permeability to a paracellular marker, Lucifer Yellow, at 72 h-exposure when compared to control group (exposed to 100 mg/dL glucose). Immunofluorescence analyses showed that glucose treatment induced a significant decrease in the tight junctional content of claudins-1 and -3 as well as a significant increase in claudin-2 (particularly at 24 h-exposure) and a time-dependent change in occludin/ZO-1 junctional content. The analyses of total cell content of these junctional proteins by Western blot did not reveal significant changes, except in claudin-2 expression. Significance: Our data suggest that high levels of glucose induce time-dependence changes in TJ structure in MDCK monolayers, suggesting a possible link between hyperglycemia-induced tubular epithelial barrier disruption and diabetic nephropathy. (AU)

• FAPESP's process: 13/15676-0 - In vitro modulation of intestinal epithelial barrier mediated by tight junctions: effect of exposure to nutrients (glucose and fatty acids), insulin and bacterial microbiota of prediabetic animals
• Grantee: Carla Beatriz Collares Buzato
• Support Opportunities: Regular Research Grants