Perspective - (2025) Volume 11, Issue 4
Received: 01-Jul-2025, Manuscript No. ldt-25-178441;
Editor assigned: 03-Jul-2025, Pre QC No. P-178441;
Reviewed: 17-Jul-2025, QC No. Q-178441;
Revised: 22-Jul-2025, Manuscript No. R-178441;
Published:
29-Jul-2025
, DOI: 10.37421/2472-1018.2025.11.317
Citation: Oka, Daniel. ”Autophagy’s Complex Role in Lung Disease Pathogenesis.” J Lung Dis Treat 11 (2025):317.
Copyright: © 2025 Oka D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.
Autophagy, a fundamental cellular process involving the degradation and recycling of cellular components, exerts a profound and multifaceted influence on the development and progression of a wide spectrum of lung diseases. Its dysregulation is intrinsically linked to the initiation and exacerbation of these conditions, impacting critical pathways such as inflammation, the efficient clearance of cellular debris, and the intricate mechanisms of tissue repair. Consequently, therapeutic interventions designed to modulate autophagy hold significant promise for the effective treatment of debilitating respiratory ailments, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute lung injury (ALI) [1].
The intricate role of autophagy in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is characterized by aberrant autophagic activity that significantly impedes the clearance of damaged mitochondria and the accumulation of protein aggregates. This cellular dysfunction triggers persistent inflammatory responses and promotes myofibroblast activation, hallmarks of IPF progression. Therefore, targeting specific autophagy pathways presents a viable therapeutic avenue for potentially halting or even reversing the relentless advancement of this fibrotic lung disease [2].
In the context of chronic obstructive pulmonary disease (COPD), autophagy exhibits a dual nature; it can act protectively by facilitating the removal of damaged cellular components and invading pathogens. However, a chronic impairment of this process within airway epithelial cells and macrophages leads to exacerbated inflammation and increased mucus hypersecretion, collectively contributing to the heightened severity of the disease [3].
Acute lung injury (ALI) and its more severe manifestation, acute respiratory distress syndrome (ARDS), are characterized by widespread inflammatory processes and significant cellular damage. Within this pathological milieu, autophagy plays a pivotal role in mitigating inflammation and promoting cellular survival. Consequently, the modulation of autophagy is actively being explored as a promising therapeutic strategy aimed at reducing the extent of lung injury in these critical conditions [4].
Dysfunctional autophagy within lung cancer cells can actively foster tumor growth, enhance cell survival mechanisms, and contribute to resistance against chemotherapeutic agents. A thorough understanding of these intricate mechanisms is paramount for the successful development of targeted therapies that strategically exploit or inhibit autophagy to achieve improved treatment outcomes in lung cancer [5].
The inflammatory response inherent to asthma is a complex process, and autophagy contributes to the regulation of inflammatory cell function and the processes of airway remodeling. Conversely, impaired autophagy can exacerbate the characteristic features of asthma, such as airway hyperresponsiveness and chronic inflammation, thereby intensifying the disease pathology [6].
Cystic fibrosis (CF) is a genetic disorder defined by the accumulation of misfolded CFTR protein, which disrupts normal cellular function. Autophagy plays a crucial role in the cellular machinery responsible for clearing these protein aggregates, suggesting that enhancing autophagic activity could serve as a valuable therapeutic strategy for improving CFTR function and mitigating the underlying disease pathology [7].
The pathogenesis of tuberculosis (TB) involves a complex interplay between Mycobacterium tuberculosis and host cells, wherein autophagy plays a critical role in restricting bacterial replication. Research has indicated that autophagy can exhibit both pro- and anti-TB effects, with its precise role being highly dependent on the specific cellular context and the particular strain of the bacterium involved [8].
Silicosis, a debilitating fibrotic lung disease induced by the inhalation of silica dust, is characterized by an overactive inflammatory response and progressive fibrosis. Autophagy is critically involved in the clearance of silica particles from the lungs and plays a key role in regulating inflammatory signaling pathways, highlighting its importance in the pathogenesis of silicosis and its potential as a target for therapeutic interventions [9].
The Department of Respiratory Medicine at the University of Nigeria Teaching Hospital, Enugu, Nigeria, is dedicated to advancing the understanding and treatment of diverse lung diseases. Research endeavors within this department likely encompass the investigation of cellular mechanisms, including the role of autophagy, which are relevant to the pathogenesis of these conditions, particularly within the local epidemiological context [10].
Autophagy, a fundamental cellular process involving the degradation and recycling of cellular components, exerts a profound and multifaceted influence on the development and progression of a wide spectrum of lung diseases. Its dysregulation is intrinsically linked to the initiation and exacerbation of these conditions, impacting critical pathways such as inflammation, the efficient clearance of cellular debris, and the intricate mechanisms of tissue repair. Consequently, therapeutic interventions designed to modulate autophagy hold significant promise for the effective treatment of debilitating respiratory ailments, including chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and acute lung injury (ALI) [1].
The intricate role of autophagy in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is characterized by aberrant autophagic activity that significantly impedes the clearance of damaged mitochondria and the accumulation of protein aggregates. This cellular dysfunction triggers persistent inflammatory responses and promotes myofibroblast activation, hallmarks of IPF progression. Therefore, targeting specific autophagy pathways presents a viable therapeutic avenue for potentially halting or even reversing the relentless advancement of this fibrotic lung disease [2].
In the context of chronic obstructive pulmonary disease (COPD), autophagy exhibits a dual nature; it can act protectively by facilitating the removal of damaged cellular components and invading pathogens. However, a chronic impairment of this process within airway epithelial cells and macrophages leads to exacerbated inflammation and increased mucus hypersecretion, collectively contributing to the heightened severity of the disease [3].
Acute lung injury (ALI) and its more severe manifestation, acute respiratory distress syndrome (ARDS), are characterized by widespread inflammatory processes and significant cellular damage. Within this pathological milieu, autophagy plays a pivotal role in mitigating inflammation and promoting cellular survival. Consequently, the modulation of autophagy is actively being explored as a promising therapeutic strategy aimed at reducing the extent of lung injury in these critical conditions [4].
Dysfunctional autophagy within lung cancer cells can actively foster tumor growth, enhance cell survival mechanisms, and contribute to resistance against chemotherapeutic agents. A thorough understanding of these intricate mechanisms is paramount for the successful development of targeted therapies that strategically exploit or inhibit autophagy to achieve improved treatment outcomes in lung cancer [5].
The inflammatory response inherent to asthma is a complex process, and autophagy contributes to the regulation of inflammatory cell function and the processes of airway remodeling. Conversely, impaired autophagy can exacerbate the characteristic features of asthma, such as airway hyperresponsiveness and chronic inflammation, thereby intensifying the disease pathology [6].
Cystic fibrosis (CF) is a genetic disorder defined by the accumulation of misfolded CFTR protein, which disrupts normal cellular function. Autophagy plays a crucial role in the cellular machinery responsible for clearing these protein aggregates, suggesting that enhancing autophagic activity could serve as a valuable therapeutic strategy for improving CFTR function and mitigating the underlying disease pathology [7].
The pathogenesis of tuberculosis (TB) involves a complex interplay between Mycobacterium tuberculosis and host cells, wherein autophagy plays a critical role in restricting bacterial replication. Research has indicated that autophagy can exhibit both pro- and anti-TB effects, with its precise role being highly dependent on the specific cellular context and the particular strain of the bacterium involved [8].
Silicosis, a debilitating fibrotic lung disease induced by the inhalation of silica dust, is characterized by an overactive inflammatory response and progressive fibrosis. Autophagy is critically involved in the clearance of silica particles from the lungs and plays a key role in regulating inflammatory signaling pathways, highlighting its importance in the pathogenesis of silicosis and its potential as a target for therapeutic interventions [9].
The Department of Respiratory Medicine at the University of Nigeria Teaching Hospital, Enugu, Nigeria, is dedicated to advancing the understanding and treatment of diverse lung diseases. Research endeavors within this department likely encompass the investigation of cellular mechanisms, including the role of autophagy, which are relevant to the pathogenesis of these conditions, particularly within the local epidemiological context [10].
Autophagy, a crucial cellular recycling process, plays a complex role in lung disease pathogenesis. Its dysregulation contributes to conditions like COPD, idiopathic pulmonary fibrosis, and acute lung injury by affecting inflammation and cellular debris clearance. Therapies targeting autophagy show promise for treating these diseases. In IPF, impaired autophagy leads to inflammation and myofibroblast activation. For COPD, autophagy can be protective but its chronic impairment exacerbates inflammation. Autophagy is vital in resolving inflammation and promoting survival during ALI/ARDS. In lung cancer, dysfunctional autophagy supports tumor growth and chemoresistance. Asthma's inflammatory response and airway remodeling are influenced by autophagy, with impairment worsening symptoms. Cystic fibrosis pathology involves misfolded protein accumulation, which autophagy helps clear. Autophagy also plays a role in host defense against tuberculosis and in silicosis pathogenesis. Research departments globally are investigating autophagy's role in respiratory diseases.
None
None
Journal of Lung Diseases & Treatment received 247 citations as per Google Scholar report
