Autophagy and airway fibrosis: Is there a link?

Abstract

In the past decade, an emerging process named "autophagy" has generated intense interest in many chronic lung diseases. Tissue remodeling and fibrosis is a common feature of many airway diseases, and current therapies do not prevent or reverse these structural changes. Autophagy has evolved as a conserved process for bulk degradation and recycling of cytoplasmic components to maintain basal cellular homeostasis and healthy organelle populations in the cell. Furthermore, autophagy serves as a cell survival mechanism and can also be induced by chemical and physical stress to the cell. Accumulating evidence demonstrates that autophagy plays an essential role in vital cellular processes, including tissue remodeling. This review will discuss some of the recent advancements made in understanding the role of this fundamental process in airway fibrosis with emphasis on airway remodeling, and how autophagy can be exploited as a target for airway remodeling in asthma and chronic obstructive pulmonary disease.

Keywords: COPD; airway mesenchymal cells; airway remodeling; asthma.

Figure 1.. Pictorial representation of the autophagy pathway.

The autophagy pathway proceeds through several phases, including initiation (formation of a preautophagosomal structure leading to an isolation membrane, or phagophore), vesicle elongation, autophagosome maturation and cargo sequestration, and autophagosome–lysosome fusion. In the final stage, autophagosomal contents are degraded by lysosomal acid hydrolases and the contents of the autolysosome are released for metabolic recycling.

Figure 2.. Autophagy mediates airway remodeling.

An altered autophagy pathway is seen in response to cellular stress in asthma and chronic obstructive pulmonary disease (allergens or smoke or genetics), leading to activation and crosstalk between structural airway and immune cells. This further leads to impairment of autophagy causing degradation of intracellular constituents, providing an energy resource for ECM protein biosynthesis, and releasing mediators of inflammation and profibrotic signaling, which collectively lead to airway remodeling in the lung. Role of circadian rhythm genes in this context needs to be investigated. ECM: extracellular matrix; TGFβ: transforming growth factor-beta.