Endotoxin- and mechanical stress–induced epigenetic changes in the regulation of the nicotinamide phosphoribosyltransferase promoter

Venkateswaran Ramamoorthi Elangovan, Sara M. Camp, Gabriel T. Kelly, Ankit A. Desai, Djanybek Adyshev, Xiaoguang Sun, Stephen Matthew Black, Ting Wang, Joe G.N. Garcia

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Mechanical ventilation, a lifesaving intervention for patients with acute respiratory distress syndrome (ARDS), also unfortunately contributes to excessive mechanical stress and impaired lung physiological and structural integrity. We have elsewhere established the pivotal role of increased nicotinamide phosphoribosyltransferase (NAMPT) transcription and secretion as well as its direct binding to the toll-like receptor 4 (TLR4) in the progression of this devastating syndrome; however, regulation of this critical gene in ventilator-induced lung injury (VILI) is not well characterized. On the basis of an emerging role for epigenetics in enrichment of VILI and CpG sites within the NAMPT promoter and 5′UTR, we hypothesized that NAMPT expression and downstream transcriptional events are influenced by epigenetic mechanisms. Concomitantly, excessive mechanical stress of human pulmonary artery endothelial cells or lipopolysaccharide (LPS) treatment led to both reduced DNA methylation levels in the NAMPT promoter and increased gene transcription. Histone deacetylase inhibition by trichostatin A or Sirt-1–silencing RNA attenuates LPS-induced NAMPT expression. Furthermore, recombinant NAMPT administration induced TLR4-dependent global H3K9 hypoacetylation. These studies suggest a complex epigenetic regulatory network of NAMPT in VILI and ARDS and open novel strategies for combating VILI and ARDS.

Original languageEnglish (US)
Pages (from-to)539-544
Number of pages6
JournalPulmonary Circulation
Volume6
Issue number4
DOIs
StatePublished - Dec 1 2016

Fingerprint

Nicotinamide Phosphoribosyltransferase
Epigenomics
Endotoxins
Ventilator-Induced Lung Injury
Adult Respiratory Distress Syndrome
Mechanical Stress
Toll-Like Receptor 4
Lipopolysaccharides
trichostatin A
Histone Deacetylases
DNA Methylation
Artificial Respiration
Pulmonary Artery
Genes
Endothelial Cells
RNA
Lung

Keywords

  • DNA methylation
  • Epigenetic modifiers
  • Epigenetics
  • Histone acetylation
  • Lung endothelium

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Elangovan, V. R., Camp, S. M., Kelly, G. T., Desai, A. A., Adyshev, D., Sun, X., ... Garcia, J. G. N. (2016). Endotoxin- and mechanical stress–induced epigenetic changes in the regulation of the nicotinamide phosphoribosyltransferase promoter. Pulmonary Circulation, 6(4), 539-544. https://doi.org/10.1086/688761

Endotoxin- and mechanical stress–induced epigenetic changes in the regulation of the nicotinamide phosphoribosyltransferase promoter. / Elangovan, Venkateswaran Ramamoorthi; Camp, Sara M.; Kelly, Gabriel T.; Desai, Ankit A.; Adyshev, Djanybek; Sun, Xiaoguang; Black, Stephen Matthew; Wang, Ting; Garcia, Joe G.N.

In: Pulmonary Circulation, Vol. 6, No. 4, 01.12.2016, p. 539-544.

Research output: Contribution to journalArticle

Elangovan, VR, Camp, SM, Kelly, GT, Desai, AA, Adyshev, D, Sun, X, Black, SM, Wang, T & Garcia, JGN 2016, 'Endotoxin- and mechanical stress–induced epigenetic changes in the regulation of the nicotinamide phosphoribosyltransferase promoter', Pulmonary Circulation, vol. 6, no. 4, pp. 539-544. https://doi.org/10.1086/688761
Elangovan, Venkateswaran Ramamoorthi ; Camp, Sara M. ; Kelly, Gabriel T. ; Desai, Ankit A. ; Adyshev, Djanybek ; Sun, Xiaoguang ; Black, Stephen Matthew ; Wang, Ting ; Garcia, Joe G.N. / Endotoxin- and mechanical stress–induced epigenetic changes in the regulation of the nicotinamide phosphoribosyltransferase promoter. In: Pulmonary Circulation. 2016 ; Vol. 6, No. 4. pp. 539-544.
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