Author:
Chung Nancy P. Y.,Khan K. M. Faisal,Andreoli Mirko,Kaner Robert J.,O’Beirne Sarah L.,Crystal Ronald G.
Abstract
AbstractWith highly active anti-retroviral therapy (HAART), higher incidence of airway abnormalities is common in the HIV population consistent with the concept of accelerated lung “aging”. Our previous findings demonstrated that HIV induces human airway basal cells (BC) into destructive and inflammatory phenotypes. Since BC function as stem/progenitor cells of the small airway epithelium (SAE), responsible for self-renewal and differentiation of SAE, we hypothesized that BC from people living with HIV (PLWH) may have altered differentiation capacity that contribute to premature aging. The data demonstrates that BC from PLWH have impaired capacity to differentiate in vitro and senescent phenotypes including shortened telomeres, increased expression of β-galactosidase and cell cycle inhibitors, and mitochondrial dysfunction. In vitro studies demonstrated that BC senescence is partly due to adverse effects of HAART on BC. These findings provide an explanation for higher incidence of airway dysfunction and accelerated lung aging observed in PLWH.
Funder
National Heart, Lung, and Blood Institute
Publisher
Springer Science and Business Media LLC
Reference105 articles.
1. Diaz, P. T. et al. Respiratory symptoms among HIV-seropositive individuals. Chest 123, 1977–1982. https://doi.org/10.1378/chest.123.6.1977 (2003).
2. Petrache, I. et al. HIV associated pulmonary emphysema: A review of the literature and inquiry into its mechanism. Thorax 63, 463–469. https://doi.org/10.1136/thx.2007.079111 (2008).
3. Deeks, S. G. & Phillips, A. N. HIV infection, antiretroviral treatment, ageing, and non-AIDS related morbidity. BMJ 338, a3172. https://doi.org/10.1136/bmj.a3172 (2009).
4. Blanco, J. R. et al. HIV infection and aging. AIDS Rev. 12, 218–230 (2010).
5. Giantsou, E. & Powrie, D. Chronic obstructive pulmonary disease in adults with human immunodeficiency virus infection: A systemic review. Health (N Y) 3, 218–227 (2011).
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献