Up‐regulation of SFTPB expression and attenuation of acute lung injury by pulmonary epithelial cell‐specific NAMPT knockdown
| Autor: | Brett A. Simon, Li Qin Zhang, Lei Wu, Guang-Liang Bi, Shamima Islam, Venkatesh Sampath, Ronald Blaine Easley, Weimin Huang, Daniel P. Heruth, Shui Qing Ye, Ding-You Li, Peixin Huang |
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| Rok vydání: | 2018 |
| Předmět: |
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 |
| Zdroj: | The FASEB Journal. 32:3583-3596 |
| ISSN: | 1530-6860 0892-6638 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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