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Paricalcitol attenuates lipopolysaccharide-induced inflammation and apoptosis in proximal tubular cells through the prostaglandin E₂ receptor EP4

Authors :
Yu Ah Hong
Keum Jin Yang
So Young Jung
Yoon Kyung Chang
Cheol Whee Park
Chul Woo Yang
Suk Young Kim
Hyeon Seok Hwang
Source :
Kidney Research and Clinical Practice, Vol 36, Iss 2, Pp 145-158 (2017)
Publication Year :
2017
Publisher :
The Korean Society of Nephrology, 2017.

Abstract

Background: Vitamin D is considered to exert a protective effect on various renal diseases but its underlying molecular mechanism remains poorly understood. This study aimed to determine whether paricalcitol attenuates inflammation and apoptosis during lipopolysaccharide (LPS)-induced renal proximal tubular cell injury through the prostaglandin E₂ (PGE₂) receptor EP4. Methods: Human renal tubular epithelial (HK-2) cells were pretreated with paricalcitol (2 ng/mL) for 1 hour and exposed to LPS (1 μg/mL). The effects of paricalcitol pretreatment in relation to an EP4 blockade using AH-23848 or EP4 small interfering RNA (siRNA) were investigated. Results: The expression of cyclooxygenase-2, PGE₂, and EP4 were significantly increased in LPS-exposed HK-2 cells treated with paricalcitol compared with cells exposed to LPS only. Paricalcitol prevented cell death induced by LPS exposure, and the cotreatment of AH-23848 or EP4 siRNA offset these cell-protective effects. The phosphorylation and nuclear translocation of p65 nuclear factor-kappaB (NF-κB) were decreased and the phosphorylation of Akt was increased in LPS-exposed cells with paricalcitol treatment. AH-23848 or EP4 siRNA inhibited the suppressive effects of paricalcitol on p65 NF-κB nuclear translocation and the activation of Akt. The production of proinflammatory cytokines and the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were attenuated by paricalcitol in LPS exposed HK-2 cells. The cotreatment with an EP4 antagonist abolished these anti-inflammatory and antiapoptotic effects. Conclusion: EP4 plays a pivotal role in anti-inflammatory and antiapoptotic effects through Akt and NF-κB signaling after paricalcitol pretreatment in LPS-induced renal proximal tubule cell injury.

Details

Language :
English, Korean
ISSN :
22119132
Volume :
36
Issue :
2
Database :
Directory of Open Access Journals
Journal :
Kidney Research and Clinical Practice
Publication Type :
Academic Journal
Accession number :
edsdoj.58dfaccd55c5484bba2ebbc2d116cb7f
Document Type :
article
Full Text :
https://doi.org/10.23876/j.krcp.2017.36.2.145