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Sci Rep. 2017 Aug 18;7(1):8856. doi: 10.1038/s41598-017-08785-2.

TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular Cells.

Lee HH1,2, Cho YI1,3, Kim SY1, Yoon YE4, Kim KS3,5, Hong SJ1,3, Han WK6,7.

Author information

1
Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, 120-752, Korea.
2
Department of Urology, National Health Insurance Service Ilsan Hospital, Gyeonggi-do, 10444, Korea.
3
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, Korea.
4
Department of Urology, Hanyang Univesity College of Medicine, Seoul, 04763, Korea.
5
Department of Biochemistry and Molecular Biology, Institute of Genetic Science, Integrated Genomic Research Center for Metabolic Regulation, Yonsei University College of Medicine, Seoul, 120-752, Korea.
6
Department of Urology, Urological Science Institute, Yonsei University College of Medicine, Seoul, 120-752, Korea. hanwk@yuhs.ac.
7
Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, 120-752, Korea. hanwk@yuhs.ac.

Abstract

Apo-A4 expression was increased in tissues from chronic kidney disease (CKD) patients compared to that in normal kidney tissue. We determined the association of apo-A4 and its regulatory signals following acute kidney injury and elucidated the effects of apo-A4 on cell signaling pathways related to kidney injury in vitro and in vivo. Tumor necrosis factor (TNF)-α, which causes inflammatory cell injury, induced significantly increased expression of apo-A4 protein levels, and these levels were related to pro-inflammatory acute kidney injury in human kidney cells. Apo-A4 expression was also increased in experimented rat kidney tissues after ischemic reperfusion injury. The expression of tumor necrosis factor receptor (TNFR) 2 was increased in both kidney cell lines and experimented rat kidney tissues following acute kidney injury. The expression of apo-A4 and TNFR2 was increased upon treatment with TNF-α. Immunohistochemistry revealed positive apo-A4 and TNFR2 staining in ischemic reperfusion injury rat kidneys compared with levels in the sham operation kidneys. After neutralization of TNF-α, NF-κB expression was only observed in the cytoplasm by immunofluorescence. Therefore, the apo-A4 expression is increased by stimulation of injured kidney cells with TNF-α and that these effects occur via a TNFR2-NFκB complex.

PMID:
28821873
PMCID:
PMC5562825
DOI:
10.1038/s41598-017-08785-2
[Indexed for MEDLINE]
Free PMC Article

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