TY - JOUR
T1 - Dysregulated Cell Signaling in Pulmonary Emphysema
AU - Lin, Chih Ru
AU - Bahmed, Karim
AU - Kosmider, Beata
N1 - Copyright © 2022 Lin, Bahmed and Kosmider.
PY - 2022/1/3
Y1 - 2022/1/3
N2 - Pulmonary emphysema is characterized by the destruction of alveolar septa and irreversible airflow limitation. Cigarette smoking is the primary cause of this disease development. It induces oxidative stress and disturbs lung physiology and tissue homeostasis. Alveolar type II (ATII) cells have stem cell potential and can repair the denuded epithelium after injury; however, their dysfunction is evident in emphysema. There is no effective treatment available for this disease. Challenges in this field involve the large complexity of lung pathophysiological processes and gaps in our knowledge on the mechanisms of emphysema progression. It implicates dysregulation of various signaling pathways, including aberrant inflammatory and oxidative responses, defective antioxidant defense system, surfactant dysfunction, altered proteostasis, disrupted circadian rhythms, mitochondrial damage, increased cell senescence, apoptosis, and abnormal proliferation and differentiation. Also, genetic predispositions are involved in this disease development. Here, we comprehensively review studies regarding dysregulated cell signaling, especially in ATII cells, and their contribution to alveolar wall destruction in emphysema. Relevant preclinical and clinical interventions are also described.
AB - Pulmonary emphysema is characterized by the destruction of alveolar septa and irreversible airflow limitation. Cigarette smoking is the primary cause of this disease development. It induces oxidative stress and disturbs lung physiology and tissue homeostasis. Alveolar type II (ATII) cells have stem cell potential and can repair the denuded epithelium after injury; however, their dysfunction is evident in emphysema. There is no effective treatment available for this disease. Challenges in this field involve the large complexity of lung pathophysiological processes and gaps in our knowledge on the mechanisms of emphysema progression. It implicates dysregulation of various signaling pathways, including aberrant inflammatory and oxidative responses, defective antioxidant defense system, surfactant dysfunction, altered proteostasis, disrupted circadian rhythms, mitochondrial damage, increased cell senescence, apoptosis, and abnormal proliferation and differentiation. Also, genetic predispositions are involved in this disease development. Here, we comprehensively review studies regarding dysregulated cell signaling, especially in ATII cells, and their contribution to alveolar wall destruction in emphysema. Relevant preclinical and clinical interventions are also described.
KW - alveolar epithelium
KW - alveolar type II cells
KW - emphysema
KW - lung
KW - oxidative stress
KW - tissue homeostasis
UR - http://www.scopus.com/inward/record.url?scp=85123165309&partnerID=8YFLogxK
U2 - 10.3389/fmed.2021.762878
DO - 10.3389/fmed.2021.762878
M3 - Review article
C2 - 35047522
AN - SCOPUS:85123165309
SN - 2296-858X
VL - 8
JO - Frontiers in Medicine
JF - Frontiers in Medicine
M1 - 762878
ER -