Renoprotective effect of paricalcitol via a modulation of the TLR4-NF-kappa B pathway in ischemia/reperfusion-induced acute kidney injury
- Lee, Jae-Won; Kim, Sun Chul; Ko, Yoon Sook; Lee, Hee Young; Cho, Eunjung; Kim, Myung-Gyu; Jo, Sang-Kyung; Cho, Won Yong; Kim, Hyoung Kyu
- Issue Date
- ACADEMIC PRESS INC ELSEVIER SCIENCE
- Acute kidney injury; NF-kappa B; Paricalcitol; Toll-like receptor 4
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, v.444, no.2, pp.121 - 127
- Journal Title
- BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
- Start Page
- End Page
- Background: The pathophysiology of ischemic acute kidney injury (AKI) is thought to include a complex interplay between vascular endothelial cell dysfunction, inflammation, and tubular cell damage. Several lines of evidence suggest a potential anti-inflammatory effect of vitamin D in various kidney injury models. In this study, we investigated the effect of paricalcitol, a synthetic vitamin D analog, on renal inflammation in a mouse model of ischemia/reperfusion (I/R) induced acute kidney injury (AKI). Methods: Paricalcitol was administered via intraperitoneal (IP) injection at 24 h before ischemia, and then I/R was performed through bilateral clamping of the renal pedicles. Twenty-four hours after I/R, mice were sacrificed for the evaluation of injury and inflammation. Additionally, an in vitro experiment using HK-2 cells was also performed to examine the direct effect of paricalcitol on tubular cells. Results: Pre-treatment with paricalcitol attenuated functional deterioration and histological damage in I/R induced AKI, and significantly decreased tissue neutrophil and macrophage infiltration and the levels of chemokines, the pro-inflammatory cytokine interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). It also decreased IR-induced upregulation of Toll-like receptor 4 (TLR4), and nuclear translocation of p65 subunit of NF-kappa B. Results from the in vitro study showed pre-treatment with paricalcitol suppressed the TNE-alpha-induced depletion of cytosolic hcB in HK-2 cells. Conclusion: These results demonstrate that pre-treatment with paricalcitol has a renoprotective effect in ischemic AKI, possibly by suppressing TLR4-NF-kappa B mediated inflammation. (C) 2014 Published by Elsevier Inc.
- Files in This Item
- There are no files associated with this item.
- Appears in
- 2. Clinical Science > Department of Nephrology and Hypertension > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.