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Endosomes and Autophagy: Regulators of Pulmonary Endothelial Cell Homeostasis in Health and Disease

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posted on 2023-08-30, 16:19 authored by Havovi Chichger, Sharon Rounds, Elizabeth O. Harrington
Significance: Alterations in oxidant/antioxidant balance injure pulmonary endothelial cells and are important in the pathogenesis of lung diseases, such as Acute Respiratory Distress Syndrome (ARDS), ischemia/reperfusion injury, pulmonary arterial hypertension (PAH), and emphysema. Critical Issues: While the role of autophagy in cellular homeostasis in pulmonary disease has been investigated, the role of the endosome in the lung vasculature is less known. Furthermore, autophagy can either decrease or exacerbate endothelial injury, depending upon inciting insult and disease process. Recent Advances: The endosomal and autophagic pathways regulate cell homeostasis. Both pathways support recycling or degradation of macromolecules or organelles, targeted to endosomes or lysosomes, respectively. Thus, both processes promote cell survival. However, with environmental stress or injury, imbalance in endosomal and autophagic pathways may enhance macromolecular or organelle degradation, diminish biosynthetic processes, and cause cell death. Future Directions: Diseases affecting the pulmonary endothelium, such as emphysema, ARDS, and PAH, are linked to altered endosomal or autophagic processing, leading to enhanced degradation of macromolecules and potential cell death. Efforts to target this imbalance have yielded limited success as treatments for lung injuries, which may be due to the complexity of both processes. It is possible that endosomal trafficking proteins, such as Rab GTPases and LAMTORs, may be novel therapeutic targets. While endocytosis or autophagy have been linked to improved function of the pulmonary endothelium in vitro and in vivo, further studies are needed to identify targets for modulating cellular homeostasis in the lung.

History

Refereed

  • Yes

Volume

31

Issue number

13

Page range

994-1008

Publication title

Antioxidants and Redox Signaling

ISSN

1557-7716

Publisher

Mary Ann Liebert

File version

  • Accepted version

Language

  • eng

Legacy posted date

2019-06-17

Legacy creation date

2019-06-17

Legacy Faculty/School/Department

Faculty of Science & Engineering

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