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The Er Stress/Upr Axis in Chronic Obstructive Pulmonary Disease and Idiopathic Pulmonary Fibrosis Publisher



Aghaei M1, 2 ; Dastghaib S3, 4 ; Aftabi S1, 5 ; Aghanoori MR6, 7 ; Alizadeh J1, 8, 9 ; Mokarram P3, 4 ; Mehrbod P10 ; Ashrafizadeh M11, 12 ; Zarrabi A12 ; Mcalinden KD13 ; Eapen MS13 ; Sohal SS13 ; Sharma P14 ; Zeki AA15, 16 Show All Authors
Authors
  1. Aghaei M1, 2
  2. Dastghaib S3, 4
  3. Aftabi S1, 5
  4. Aghanoori MR6, 7
  5. Alizadeh J1, 8, 9
  6. Mokarram P3, 4
  7. Mehrbod P10
  8. Ashrafizadeh M11, 12
  9. Zarrabi A12
  10. Mcalinden KD13
  11. Eapen MS13
  12. Sohal SS13
  13. Sharma P14
  14. Zeki AA15, 16
  15. Ghavami S1, 4, 8, 9
Show Affiliations
Authors Affiliations
  1. 1. Department of Human Anatomy and Cell Science, Rady Faculty of Health Sciences, Max Rady College of Medicine, University of Manitoba, Winnipeg, R3E 0J9, MB, Canada
  2. 2. Department of Clinical Biochemistry, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, 8174673461, Iran
  3. 3. Department of Clinical Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, 7134845794, Iran
  4. 4. Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, 7134845794, Iran
  5. 5. Medical Physics Department, Cancer Care Manitoba, University of Manitoba, Winnipeg, R3E 0V9, MB, Canada
  6. 6. Division of Neurodegenerative Disorders, St Boniface Hospital Albrechtsen Research Centre, University of Manitoba, Winnipeg, R2H 2A6, MB, Canada
  7. 7. Department of Internal Medicine, University of Manitoba, Winnipeg, R3E 0V9, MB, Canada
  8. 8. Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, R3E 0V9, MB, Canada
  9. 9. Biology of Breathing Theme, Children Hospital Research Institute of Manitoba, University of Manitoba, Winnipeg, R3E 0V9, MB, Canada
  10. 10. Influenza and Respiratory Viruses Department, Pasteur Institute of Iran, Tehran, 1316943551, Iran
  11. 11. Faculty of Engineering and Natural Sciences, Sabanci University, Orta Mahalle, Universite Caddesi No. 27, Orhanli, Tuzla, 34956, Istanbul, Turkey
  12. 12. Sabanci University, Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956, Istanbul, Turkey
  13. 13. Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, University of Tasmania, Tasmania, Launceston, 7250, Australia
  14. 14. Center for Translational Medicine, Jane & Leonard Korman Respiratory Institute, Thomas Jefferson University, Philadelphia, 19107, PA, United States
  15. 15. Davis School of Medicine, Department of Internal Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, UC Davis Lung Center, University of California, Davis, 95616, CA, United States
  16. 16. Veterans Affairs Medical Center, Mather, 95655, CA, United States

Source: Life Published:2021


Abstract

Cellular protein homeostasis in the lungs is constantly disrupted by recurrent exposure to various external and internal stressors, which may cause considerable protein secretion pressure on the endoplasmic reticulum (ER), resulting in the survival and differentiation of these cell types to meet the increased functional demands. Cells are able to induce a highly conserved adaptive mechanism, known as the unfolded protein response (UPR), to manage such stresses. UPR dysregulation and ER stress are involved in numerous human illnesses, such as metabolic syndrome, fibrotic diseases, and neurodegeneration, and cancer. Therefore, effective and specific compounds targeting the UPR pathway are being considered as potential therapies. This review focuses on the impact of both external and internal stressors on the ER in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) and discusses the role of the UPR signaling pathway activation in the control of cellular damage and specifically highlights the potential involvement of non-coding RNAs in COPD. Summaries of pathogenic mechanisms associated with the ER stress/UPR axis contributing to IPF and COPD, and promising pharmacological intervention strategies, are also presented. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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