Activation of alveolar epithelial ER stress by β-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure-Reference-Cited by-同舟云学术

Activation of alveolar epithelial ER stress by β-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure

Published:2024-08-01 Issue:2 Volume:327 Page:L232-L249
ISSN:1040-0605
Container-title:American Journal of Physiology-Lung Cellular and Molecular Physiology
language:en
Short-container-title:American Journal of Physiology-Lung Cellular and Molecular Physiology

Author:

Murthy Aditi¹²,Rodriguez Luis R.¹²,Dimopoulos Thalia¹,Bui Sarah¹²,Iyer Swati¹,Chavez Katrina¹,Tomer Yaniv¹,Abraham Valsamma¹,Cooper Charlotte¹,Renner David M.³⁴^ORCID,Katzen Jeremy B.¹²,Bentley Ian D.⁵,Ghadiali Samir N.⁶⁷^ORCID,Englert Joshua A.⁵^ORCID,Weiss Susan R.³⁴^ORCID,Beers Michael F.¹²^ORCID

Affiliation:

1. Pulmonary and Critical Care Division, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States

2. PENN-CHOP Lung Biology Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States

3. Department of Microbiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States

4. Penn Center for Research on Coronaviruses and Emerging Pathogens, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, United States

5. Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

6. Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

7. Department of Biomedical Engineering, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Abstract

COVID-19 syndrome is characterized by hypoxemic respiratory failure and high mortality. In this report, we use two murine models to show that β-coronavirus infection produces acute lung injury, which results from an aberrant host response, activating multiple epithelial endoplasmic reticular stress pathways, disrupting pulmonary surfactant metabolism and function, and forcing emergence of an aberrant epithelial transition state. Our results offer a mechanistic link between SARS-CoV-2 infection, AT2 cell biology, and respiratory failure.

Funder

HHS | NIH | NIAID | Division of Microbiology and Infectious Diseases

HHS | NIH | National Heart, Lung, and Blood Institute

U.S. Department of Veterans Affairs

Publisher

American Physiological Society

Link

https://journals.physiology.org/doi/pdf/10.1152/ajplung.00324.2023

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