Skip to main content

LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4.

Publication ,  Journal Article
Zhou, H; Simion, V; Pierce, JB; Haemmig, S; Chen, AF; Feinberg, MW
Published in: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
January 2021

Chronic vascular inflammation plays a key role in the pathogenesis of atherosclerosis. Long non-coding RNAs (lncRNAs) have emerged as essential inflammation regulators. We identify a novel lncRNA termed lncRNA-MAP3K4 that is enriched in the vessel wall and regulates vascular inflammation. In the aortic intima, lncRNA-MAP3K4 expression was reduced by 50% during the progression of atherosclerosis (chronic inflammation) and 70% during endotoxemia (acute inflammation). lncRNA-MAP3K4 knockdown reduced the expression of key inflammatory factors (eg, ICAM-1, E-selectin, MCP-1) in endothelial cells or vascular smooth muscle cells and decreased monocytes adhesion to endothelium, as well as reducing TNF-α, IL-1β, COX2 expression in macrophages. Mechanistically, lncRNA-MAP3K4 regulates inflammation through the p38 MAPK signaling pathway. lncRNA-MAP3K4 shares a bidirectional promoter with MAP3K4, an upstream regulator of the MAPK signaling pathway, and regulates its transcription in cis. lncRNA-MAP3K4 and MAP3K4 show coordinated expression in response to inflammation in vivo and in vitro. Similar to lncRNA-MAP3K4, MAP3K4 knockdown reduced the expression of inflammatory factors in several different vascular cells. Furthermore, lncRNA-MAP3K4 and MAP3K4 knockdown showed cooperativity in reducing inflammation in endothelial cells. Collectively, these findings unveil the role of a novel lncRNA in vascular inflammation by cis-regulating MAP3K4 via a p38 MAPK pathway.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

DOI

EISSN

1530-6860

ISSN

0892-6638

Publication Date

January 2021

Volume

35

Issue

1

Start / End Page

e21133

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Vasculitis
  • RNA, Long Noncoding
  • Mice
  • MAP Kinase Signaling System
  • MAP Kinase Kinase Kinase 4
  • Inflammation
  • Gene Expression Regulation
  • Cell Line
  • Biochemistry & Molecular Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhou, H., Simion, V., Pierce, J. B., Haemmig, S., Chen, A. F., & Feinberg, M. W. (2021). LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 35(1), e21133. https://doi.org/10.1096/fj.202001654rr
Zhou, Haoyang, Viorel Simion, Jacob B. Pierce, Stefan Haemmig, Alex F. Chen, and Mark W. Feinberg. “LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4.FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology 35, no. 1 (January 2021): e21133. https://doi.org/10.1096/fj.202001654rr.
Zhou H, Simion V, Pierce JB, Haemmig S, Chen AF, Feinberg MW. LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2021 Jan;35(1):e21133.
Zhou, Haoyang, et al. “LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4.FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 35, no. 1, Jan. 2021, p. e21133. Epmc, doi:10.1096/fj.202001654rr.
Zhou H, Simion V, Pierce JB, Haemmig S, Chen AF, Feinberg MW. LncRNA-MAP3K4 regulates vascular inflammation through the p38 MAPK signaling pathway and cis-modulation of MAP3K4. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2021 Jan;35(1):e21133.

Published In

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

DOI

EISSN

1530-6860

ISSN

0892-6638

Publication Date

January 2021

Volume

35

Issue

1

Start / End Page

e21133

Related Subject Headings

  • p38 Mitogen-Activated Protein Kinases
  • Vasculitis
  • RNA, Long Noncoding
  • Mice
  • MAP Kinase Signaling System
  • MAP Kinase Kinase Kinase 4
  • Inflammation
  • Gene Expression Regulation
  • Cell Line
  • Biochemistry & Molecular Biology