5-Aza-2'-deoxycytidine protects against emphysema in mice via suppressing p16Ink4a expression in lung tissue.

Abstract

BACKGROUND:

There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs) contribute to neovascularization and play an important role in the development of COPD. The gene for p16Ink4a is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16Ink4a in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE), and further to search for a potential candidate agent protecting against emphysema induced by CSE.

MATERIALS AND METHODS:

An animal emphysema model was induced by intraperitoneal injection of CSE. 5-Aza-2'-deoxycytidine (5-Aza-CdR) was administered to the emphysematous mice. Lung function and histomorphology of lung tissue were measured. The p16Ink4a protein and mRNA in EPCs and lung tissues were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction, respectively.

RESULTS:

CSE induced emphysema with increased p16Ink4a expression in lung tissue and bone marrow-derived EPCs. 5-Aza-CdR partly protected against emphysema, especially in the lung-morphology profile, and partly protest against the overexpression of p16Ink4a in EPCs and lung tissue induced by CSE.

CONCLUSION:

5-Aza-CdR partly protected against emphysema in mice via suppressing p16Ink4a expression in EPCs and lung tissue.

• Authors: Zhi-Hui He, Yan Chen, Ping Chen, Sheng-Dong He, Hui-Hui Zeng, Ji-Ru Ye, Da Liu, Jun Cao
• Journal: International journal of chronic obstructive pulmonary disease (Int J Chron Obstruct Pulmon Dis) Vol. 12 Pg. 3149-3158 ( 2017) ISSN: 1178-2005 [Electronic] New Zealand
• PMID: 29133977 (Publication Type: Journal Article)

Chemical References

• Cdkn2a protein, mouse
• Cyclin-Dependent Kinase Inhibitor p16
• Smoke
• Decitabine
• Azacitidine

Topics

• Animals
• Azacitidine (analogs & derivatives, pharmacology)
• Cells, Cultured
• Cigarette Smoking (adverse effects)
• Cyclin-Dependent Kinase Inhibitor p16 (metabolism)
• Cytoprotection
• Decitabine
• Disease Models, Animal
• Down-Regulation
• Endothelial Progenitor Cells (drug effects, metabolism, pathology)
• Lung (drug effects, metabolism, pathology)
• Male
• Mice, Inbred C57BL
• Pulmonary Emphysema (metabolism, pathology, prevention & control)
• Signal Transduction (drug effects)
• Smoke (adverse effects)