TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular Cells
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 re...
Main Authors: | , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2017-08-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-017-08785-2 |
_version_ | 1818841586308481024 |
---|---|
author | Hyung Ho Lee Young In Cho Sook Young Kim Young Eun Yoon Kyung Sup Kim Sung Joon Hong Woong Kyu Han |
author_facet | Hyung Ho Lee Young In Cho Sook Young Kim Young Eun Yoon Kyung Sup Kim Sung Joon Hong Woong Kyu Han |
author_sort | Hyung Ho Lee |
collection | DOAJ |
description | 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. |
first_indexed | 2024-12-19T04:28:26Z |
format | Article |
id | doaj.art-c8fa8d5f8cd1497b828431a94fe8fe3d |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-12-19T04:28:26Z |
publishDate | 2017-08-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Scientific Reports |
spelling | doaj.art-c8fa8d5f8cd1497b828431a94fe8fe3d2022-12-21T20:35:57ZengNature PortfolioScientific Reports2045-23222017-08-01711910.1038/s41598-017-08785-2TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular CellsHyung Ho Lee0Young In Cho1Sook Young Kim2Young Eun Yoon3Kyung Sup Kim4Sung Joon Hong5Woong Kyu Han6Department of Urology, Urological Science Institute, Yonsei University College of MedicineDepartment of Urology, Urological Science Institute, Yonsei University College of MedicineDepartment of Urology, Urological Science Institute, Yonsei University College of MedicineDepartment of Urology, Hanyang Univesity College of MedicineBrain Korea 21 PLUS Project for Medical Science, Yonsei University College of MedicineDepartment of Urology, Urological Science Institute, Yonsei University College of MedicineDepartment of Urology, Urological Science Institute, Yonsei University College of MedicineAbstract 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.https://doi.org/10.1038/s41598-017-08785-2 |
spellingShingle | Hyung Ho Lee Young In Cho Sook Young Kim Young Eun Yoon Kyung Sup Kim Sung Joon Hong Woong Kyu Han TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular Cells Scientific Reports |
title | TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular Cells |
title_full | TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular Cells |
title_fullStr | TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular Cells |
title_full_unstemmed | TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular Cells |
title_short | TNF-α-induced Inflammation Stimulates Apolipoprotein-A4 via Activation of TNFR2 and NF-κB Signaling in Kidney Tubular Cells |
title_sort | tnf α induced inflammation stimulates apolipoprotein a4 via activation of tnfr2 and nf κb signaling in kidney tubular cells |
url | https://doi.org/10.1038/s41598-017-08785-2 |
work_keys_str_mv | AT hyungholee tnfainducedinflammationstimulatesapolipoproteina4viaactivationoftnfr2andnfkbsignalinginkidneytubularcells AT youngincho tnfainducedinflammationstimulatesapolipoproteina4viaactivationoftnfr2andnfkbsignalinginkidneytubularcells AT sookyoungkim tnfainducedinflammationstimulatesapolipoproteina4viaactivationoftnfr2andnfkbsignalinginkidneytubularcells AT youngeunyoon tnfainducedinflammationstimulatesapolipoproteina4viaactivationoftnfr2andnfkbsignalinginkidneytubularcells AT kyungsupkim tnfainducedinflammationstimulatesapolipoproteina4viaactivationoftnfr2andnfkbsignalinginkidneytubularcells AT sungjoonhong tnfainducedinflammationstimulatesapolipoproteina4viaactivationoftnfr2andnfkbsignalinginkidneytubularcells AT woongkyuhan tnfainducedinflammationstimulatesapolipoproteina4viaactivationoftnfr2andnfkbsignalinginkidneytubularcells |