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Autophagy: catabolism at the crossroads of lung epithelial homeostasis and influenza pathogenesis.

Hahn, David R
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725116

Abstract Details

2014, PhD, University of Cincinnati, Medicine: Molecular and Developmental Biology.
The autophagic pathway is recognized as important for general cellular homeostasis through metabolite recycling and degradation of cytotoxic protein aggregates or damaged organelles. Recent studies have established that the requirement for basal autophagy is largely tissue specific and hint at an emerging, complex role in pathogen infection. To assess the functional significance of autophagy in lung epithelial development, homeostasis, and viral challenge, we generated genetic mouse models for loss of autophagic function in the lung epithelium. Loss of >90% of autophagic function throughout the lung epithelium resulted in septal thickening and altered lung mechanics in aged mice. In young adult mice however, this degree of ablation did not alter alveolar homeostasis but did result in altered bronchiolar cell morphology. Further, a loss of up to 50% of autophagic function was both stable and well tolerated throughout the murine life span and significantly reduced the replication of influenza A/H3N2 virus and associated morbidity/mortality. Collectively these results suggest that disruption of autophagy in the lung epithelium may be an effective means to combat the spread of influenza A virus strains; however additional study is needed to determine if the safety and efficacy reported here extends to other subtypes and strains of influenza.
Timothy Weaver, Ph.D. (Committee Chair)
Raymond Boissy, D.Sc. (Committee Member)
Xinhua Lin, Ph.D. (Committee Member)
John Shannon, Ph.D. (Committee Member)
James Wells, Ph.D. (Committee Member)
95 p.
Molecular Biology
Autophagy; Lung; Epithelium; Influenza; Homeostasis; Cilia

Recommended Citations

Citations

  • Hahn, D. R. (2014). Autophagy: catabolism at the crossroads of lung epithelial homeostasis and influenza pathogenesis. [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725116

    APA Style (7th edition)

  • Hahn, David. Autophagy: catabolism at the crossroads of lung epithelial homeostasis and influenza pathogenesis. 2014. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725116.

    MLA Style (8th edition)

  • Hahn, David. "Autophagy: catabolism at the crossroads of lung epithelial homeostasis and influenza pathogenesis." Doctoral dissertation, University of Cincinnati, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1394725116

    Chicago Manual of Style (17th edition)

ucin1394725116
229
© 2014, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.