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

Hyung Ho Lee, Young In Cho, Sook Young Kim, Young Eun Yoon, Kyung Sup Kim, Sung Joon Hong, Woong Kyu Han

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11 Citations (Scopus)


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.

Original languageEnglish
Article number8856
JournalScientific reports
Issue number1
Publication statusPublished - 2017 Dec 1

Bibliographical note

Funding Information:
This study was financially supported by the “Kiturami” Faculty Research Assistance Program of Yonsei University College of Medicine for 2014(6-2014-0151).

Publisher Copyright:
© 2017 The Author(s).

All Science Journal Classification (ASJC) codes

  • General


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