DPP-4 inhibitor attenuates toxic effects of indoxyl sulfate on kidney tubular cells

Wei Jie Wang, Chen Hung Chang, Mao Feng Sun, Sheng Feng Hsu, Ching Sung Weng

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Diabetic nephropathy is a common causative factor of chronic kidney disease (CKD). DPP-4 inhibitor has the ability to improve kidney function and renal microvasculature. In the present study, we investigate the deleterious effects of IS on proximal tubular cells and the protective role of DPP-4 inhibitor. Human kidney 2 (HK-2) cells were exposed to IS in the presence or absence of DPP-4 inhibitor. Effects of DPP-4 inhibitor on viability of HK-2 cells were determined by MTT assay. Reactive oxygen species (ROS) production was examined using fluorescent microscopy. Levels of cleaved caspase-3, transforming growth factor-beta (TGF-β), α-smooth muscle actin (α-SMA) and NF-kappaB p65 and phosphorylation of AKT and extracellular signal-regulated kinase (ERK) were detected by immunoblotting. Production of ROS and level of cleaved caspase-3 were increased by IS in a dose-dependent manner. The phosphorylation of AKT and ERK p65 were decreased alongside activation of NF-κB. Expression of TGF-β and α-SMA, were upregulated in IS-treated HK-2 cells. Treatment with DPP-4 inhibitor resulted in a significant increase in cell viability and a decrease of ROS production in IS-treated HK-2 cells. DPP-4 inhibitor restored IS-induced deactivations of AKT and ERK and inhibited activation of NF-κB in IS-treated HK-2 cells. Moreover, DPP-4 inhibitor could also attenuate IS-induced up-regulation of TGF-β and α-SMA expression. These findings suggest that DPP-4 inhibitor possesses anti-apoptotic activity to ameliorate the IS-induced renal damage, which may be partly attributed to regulating ROS/p38MAPK/ERK and PI3K-AKT pathways as well as downstream NF-κB signaling pathway.

Original languageEnglish (US)
Article numbere93447
JournalPloS one
Volume9
Issue number4
DOIs
StatePublished - Apr 22 2014

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Indican
Poisons
Extracellular Signal-Regulated MAP Kinases
kidney cells
Reactive Oxygen Species
sulfates
kidneys
Transforming Growth Factor beta
Kidney
Phosphorylation
mitogen-activated protein kinase
reactive oxygen species
Caspase 3
transforming growth factor beta
Chemical activation
cells
caspase-3
NF-kappa B
Phosphatidylinositol 3-Kinases
phosphorylation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wang, W. J., Chang, C. H., Sun, M. F., Hsu, S. F., & Weng, C. S. (2014). DPP-4 inhibitor attenuates toxic effects of indoxyl sulfate on kidney tubular cells. PloS one, 9(4), [e93447]. https://doi.org/10.1371/journal.pone.0093447

DPP-4 inhibitor attenuates toxic effects of indoxyl sulfate on kidney tubular cells. / Wang, Wei Jie; Chang, Chen Hung; Sun, Mao Feng; Hsu, Sheng Feng; Weng, Ching Sung.

In: PloS one, Vol. 9, No. 4, e93447, 22.04.2014.

Research output: Contribution to journalArticle

Wang, Wei Jie ; Chang, Chen Hung ; Sun, Mao Feng ; Hsu, Sheng Feng ; Weng, Ching Sung. / DPP-4 inhibitor attenuates toxic effects of indoxyl sulfate on kidney tubular cells. In: PloS one. 2014 ; Vol. 9, No. 4.
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