Sitagliptin protects renal glomerular endothelial cells against high glucose-induced dysfunction and injury

Abstract

Sitagliptin is a well-established anti-diabetic drug that also exerts protective effects on diabetic complications. Previous work reveals that sitagliptin has a protective effect on diabetic nephropathy (DN). Vascular impairment frequently occurs in diabetic renal complications. Here, we evaluated the protective function of sitagliptin in human renal glomerular endothelial cells (HrGECs) under high glucose (HG) conditions. Expressions of the pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-8 (IL-8) were assessed using real-time PCR and ELISA. Endothelial cells permeability was assayed using the fluorescein isothiocyanate dextran (FITC-dextran) and trans-endothelial electrical resistance (TEER) assay. The results show that sitagliptin mitigated HG-induced oxidative stress in HrGECs with decreased levels of mitochondrial reactive oxygen species (ROS), Malondialdehyde (MDA), and 8-hydroxydeoxyguanosine (8-OHdG). Sitagliptin inhibited HG-induced production of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-8 (IL-8) in HrGECs. It also ameliorated HG-induced aggravation of HrGECs permeability and reduction of the tight junction component claudin-5. Moreover, kruppel Like Factor 6 (KLF6) mediated the protective effects of sitagliptin on endothelial monolayer permeability against HG. Collectively, sitagliptin reversed the HG-induced oxidative stress, inflammation, and increased permeability in HrGECs via regulating KLF6. This study suggests that sitagliptin might be implicated as an effective strategy for preventing diabetic renal injuries in the future.

FGF-2 enhances fibrogenetic changes in TGF-β2 treated human conjunctival fibroblasts

“…The TEER values for HconF cell monolayers were determined using a TEER plate (0.4 μm pore size and 12 mm diameter; Corning Transwell, Sigma-Aldrich) and an electrical resistance system (KANTO CHEMICAL CO. INC., Tokyo, Japan) as described in a previous study 26 , 30 . Alternatively, FITC-dextran permeability measurements were conducted by measuring the fluorescence intensity of the amount of FITC that permeated through the membrane from the basal compartment to the apical compartment during a period of 60 min, as described in a recent report 31 .…”

The Selective α1 Antagonist Tamsulosin Alters ECM Distributions and Cellular Metabolic Functions of ARPE 19 Cells in a Concentration-Dependent Manner

“…ARPE 19 cell monolayers were cultured in a TEER plate (0.4 μm pore size and 12 mm diameter; Corning Transwell, Sigma-Aldrich, St. Louis, MA, USA) and analyzed by (1) scanning electron microscopy using HITACHI S-4300 microscope operated at 5 keV (the detector features 1280 × 960 pixel), (2) the TEER values (Ωcm 2 ) using an electrical resistance system (KANTO CHEMICAL CO. INC., Tokyo, Japan) and (3) FITC-dextran permeability measurements by measuring the fluorescence intensity of the amount of FITC that permeated through the membrane from the basal compartment to the apical compartment during a period of 60 min as described in a previous study [ 27 , 28 , 29 ].…”

Biochemical Investigation of Therapeutic Potentials of Plant-Based Bioactive Compounds as Stimulators of Glucagon like peptide-1 Secretion

“…Interestingly, many recent studies have investigated the antioxidant and anti-inflammatory effects of these inhibitors. 6 - 13 …”

“…Interestingly, many recent studies have investigated the antioxidant and antiinflammatory effects of these inhibitors. [6][7][8][9][10][11][12][13] Further, many antioxidants, anti-inflammatory, and antiinfective bioactive compounds have been studied to be effective biocontrols against animal and human diseases including zoonotic conditions of intestine. 3,[14][15][16][17][18] Nevertheless, antioxidants are mostly present in fruits and vegetable and possess great potential against oxidative damage.…”