Back to Search
Start Over
Up‐regulation of SFTPB expression and attenuation of acute lung injury by pulmonary epithelial cell‐specific NAMPT knockdown
- Source :
- The FASEB Journal. 32:3583-3596
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- Although a deficiency of surfactant protein B (SFTPB) has been associated with lung injury, SFTPB expression has not yet been linked with nicotinamide phosphoribosyltransferase (NAMPT), a potential biomarker of acute lung injury (ALI). The effects of Nampt in the pulmonary epithelial cell on both SFTPB expression and lung inflammation were investigated in a LPS-induced ALI mouse model. Pulmonary epithelial cell-specific knockdown of Nampt gene expression, achieved by the crossing of Nampt gene exon 2 floxed mice with mice expressing epithelial-specific transgene Cre or by the use of epithelial-specific expression of anti-Nampt antibody cDNA, significantly attenuated LPS-induced ALI. Knockdown of Nampt expression was accompanied by lower levels of bronchoalveolar lavage (BAL) neutrophil infiltrates, total protein and TNF-α levels, as well as lower lung injury scores. Notably, Nampt knockdown was also associated with significantly increased BAL SFTPB levels relative to the wild-type control mice. Down-regulation of NAMPT increased the expression of SFTPB and rescued TNF-α-induced inhibition of SFTPB, whereas overexpression of NAMPT inhibited SFTPB expression in both H441 and A549 cells. Inhibition of NAMPT up-regulated SFTPB expression by enhancing histone acetylation to increase its transcription. Additional data indicated that these effects were mainly mediated by NAMPT nonenzymatic function via the JNK pathway. This study shows that pulmonary epithelial cell-specific knockdown of NAMPT expression attenuated ALI, in part, via up-regulation of SFTPB expression. Thus, epithelial cell-specific knockdown of Nampt may be a potential new and viable therapeutic modality to ALI.-Bi, G., Wu, L., Huang, P., Islam, S., Heruth, D. P., Zhang, L. Q., Li, D.-Y., Sampath, V., Huang, W., Simon, B. A., Easley, R. B., Ye, S. Q. Up-regulation of SFTPB expression and attenuation of acute lung injury by pulmonary epithelial cell-specific NAMPT knockdown.
- Subjects :
- 0301 basic medicine
MAP Kinase Kinase 4
Acute Lung Injury
Nicotinamide phosphoribosyltransferase
Lung injury
Biochemistry
Histones
Mice
03 medical and health sciences
chemistry.chemical_compound
NAMPT Gene
Downregulation and upregulation
Cell Line, Tumor
Gene expression
Genetics
Animals
Humans
Medicine
Nicotinamide Phosphoribosyltransferase
Molecular Biology
A549 cell
Gene knockdown
medicine.diagnostic_test
Tumor Necrosis Factor-alpha
business.industry
Research
Pulmonary Surfactants
respiratory system
Up-Regulation
respiratory tract diseases
Mice, Inbred C57BL
030104 developmental biology
Bronchoalveolar lavage
chemistry
Alveolar Epithelial Cells
Cancer research
Cytokines
business
Biotechnology
Subjects
Details
- ISSN :
- 15306860 and 08926638
- Volume :
- 32
- Database :
- OpenAIRE
- Journal :
- The FASEB Journal
- Accession number :
- edsair.doi.dedup.....fb0e84a358b27d4c7e4ea94cd7abd77d