CR6 interacting factor 1 deficiency promotes endothelial inflammation by SIRT1 downregulation

Shuyu Piao; Jun Wan Lee; Harsha Nagar; Saet-Byel Jung; Sujeong Choi; Seonhee Kim; Ikjun Lee; Sung-Min Kim; Nara Shin; Yu Ran Lee; Sang Do Lee; Jin Bong Park; Kaikobad Irani; Minho Won; Gang Min Hur; Byeong Hwa Jeon; Dong Woon Kim; Cuk-Seong Kim

doi:10.1371/journal.pone.0192693

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CR6 interacting factor 1 deficiency promotes endothelial inflammation by SIRT1 downregulation

Journal article

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CR6 interacting factor 1 deficiency promotes endothelial inflammation by SIRT1 downregulation

Shuyu Piao, Jun Wan Lee, Harsha Nagar, Saet-Byel Jung, Sujeong Choi, Seonhee Kim, Ikjun Lee, Sung-Min Kim, Nara Shin, Yu Ran Lee, …

PloS one, Vol.13(2), e0192693

2018

DOI: 10.1371/journal.pone.0192693

PMCID: PMC5825004

PMID: 29474366

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Abstract

Aims CR6 interacting factor 1 (CRIF1) deficiency impairs mitochondrial oxidative phosphorylation complexes, contributing to increased mitochondrial and cellular reactive oxygen species (ROS) production. CRIF1 downregulation has also been revealed to decrease sirtuin 1 (SIRT1) expression and impair vascular function. Inhibition of SIRT1 disturbs oxidative energy metabolism and stimulates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-induced inflammation. Therefore, we hypothesized that both CRIF1 deficiency-induced mitochondrial ROS production and SIRT1 reduction play stimulatory roles in vascular inflammation. Methods and results Plasma levels and mRNA expression of proinflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6) were markedly elevated in endothelium-specific CRIF1-knockout mice and CRIF1-silenced endothelial cells, respectively. Moreover, CRIF1 deficiency-induced vascular adhesion molecule-1 (VCAM-1) expression was consistently attenuated by the antioxidant N-acetyl-cysteine and NF-κB inhibitor (BAY11). We next showed that siRNA-mediated CRIF1 downregulation markedly activated NF-κB. SIRT1 overexpression not only rescued CRIF1 deficiency-induced NF-κB activation but also decreased inflammatory cytokines (TNF-α, IL-1β, and IL-6) and VCAM-1 expression levels in endothelial cells. Conclusions These results strongly suggest that CRIF1 deficiency promotes endothelial cell inflammation by increasing VCAM-1 expression, elevating inflammatory cytokines levels, and activating the transcription factor NF-κB, all of which were inhibited by SIRT1 overexpression.

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Title: Subtitle: CR6 interacting factor 1 deficiency promotes endothelial inflammation by SIRT1 downregulation
Creators: Shuyu Piao - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Jun Wan Lee - Emergency ICU, Regional Emergency Center, Chungnam National University Hospital, Daejeon, Republic of Korea
Harsha Nagar - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Saet-Byel Jung - Department of Endocrinology, Chungnam National University Hospital, Daejeon, Republic of Korea
Sujeong Choi - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Seonhee Kim - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Ikjun Lee - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Sung-Min Kim - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Nara Shin - Department of Anatomy & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Yu Ran Lee - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Sang Do Lee - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Jin Bong Park - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Kaikobad Irani - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA United States of America
Minho Won - Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Gang Min Hur - Department of Pharmacology, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Byeong Hwa Jeon - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Dong Woon Kim - Department of Anatomy & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Cuk-Seong Kim - Department of physiology & Medical Science, School of Medicine, Chungnam National University, Daejeon, Republic of Korea
Resource Type: Journal article
Publication Details: PloS one, Vol.13(2), e0192693
DOI: 10.1371/journal.pone.0192693
PMID: 29474366
PMCID: PMC5825004
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: name: Korea Health Technology R&D Project, award: HI17C-1202-010017
Language: English
Date published: 2018
Academic Unit: Cardiovascular Medicine; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984047886802771

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