16 December 2016 : Original article
Sirtuin1 (SIRT1) Regulates Tumor Necrosis Factor-alpha (TNF-α-Induced) Aquaporin-2 (AQP2) Expression in Renal Medullary Collecting Duct Cells Through Inhibiting the NF-κB Pathway
Qinqin Lin1ABCDEFG*, Yuanwen Geng1BCDE, Shuaishuai Lin2BCDEF, Zhenjun Tian3ABCDEFGDOI: 10.12659/MSMBR.901909
Med Sci Monit Basic Res 2016; 22:165-174
Abstract
BACKGROUND: Aquaporin-2 (AQP2) plays a major role in water reabsorption in the renal collecting duct, and is involved in a variety of renal disease. Recent studies have indicate that sirtuin1 (SIRT1) exerts renoprotective properties against kidney diseases. This study aimed to determine the potential role of SIRT1 in AQP2 expression induced by tumor necrosis factor-alpha (TNF-α) and to disclose the underlying mechanism in renal inner medullary collecting duct (IMCD) cells.
MATERIAL AND METHODS: Quantitative real-time PCR and Western blotting were respectively identified mRNA and protein expression. Immunofluorescence staining was used to detect the localization of AQP2. Small-interfering RNA (siRNA) was carried out for mechanism study.
RESULTS: Results showed that AQP2 was clearly increased in the plasma membrane and decreased in the cytoplasm of IMCD cells treated with AVP. TNF-α treatment in IMCD cells significantly reduced SIRT1 and AQP2 expression, and increased acetylated NF-κBp65 protein level in time- and concentration-dependent manners. Moreover, SIRT1 overexpression or the activator SRT1720 augmented AQP2 expression and reduced the acetylation of NF-κBp65, which was reversed by SIRT1 siRNA or the inhibitors Ex527 and sirtinol in TNF-α-induced IMCD cells. Knockdown of NF-κBp65 or NF-κBp65 inhibition by pyrrolidine dithiocarbamate (PDTC) enhanced AQP2 expression in IMCD cells exposed to TNF-α. Importantly, knockdown of NF-kBp65 augmented the up-regulation of SIRT1 on AQP2 expression in IMCD cells induced by TNF-α.
CONCLUSIONS: These findings indicate that SIRT1 increases AQP2 expression in TNF-α-induced IMCD cells via the NF-κB-dependent signalling pathway, which might provide novel insight to understanding the renoprotective effects of SIRT1 in kidney diseases.
Keywords: Aquaporin 2, Kidney Tubules, Collecting
Most Viewed Current Articles
15 Jun 2022 : Clinical Research
Evaluation of Apical Leakage After Root Canal Obturation with Glass Ionomer, Resin, and Zinc Oxide Eugenol ...DOI :10.12659/MSMBR.936675
Med Sci Monit Basic Res 2022; 28:e936675
07 Jul 2022 : Laboratory Research
Cytotoxicity, Apoptosis, Migration Inhibition, and Autophagy-Induced by Crude Ricin from Ricinus communis S...DOI :10.12659/MSMBR.936683
Med Sci Monit Basic Res 2022; 28:e936683
01 Jun 2022 : Laboratory Research
Comparison of Sealing Abilities Among Zinc Oxide Eugenol Root-Canal Filling Cement, Antibacterial Biocerami...DOI :10.12659/MSMBR.936319
Med Sci Monit Basic Res 2022; 28:e936319
08 Dec 2022 : Original article
Use of Estimated Glomerular Filtration Rate and Urine Albumin-to-Creatinine Ratio Based on KDIGO 2012 Guide...DOI :10.12659/MSMBR.938176
Med Sci Monit Basic Res 2022; 28:e938176