Matrix remodeling in chronic lung diseases

Abstract

Multicellular organisms synthesize and renew components of their subcellular and scaffolding proteins, collectively known as the extracellular matrix molecules (ECMs). In the lung, ECMs maintain tensile strength, elasticity, and dictate the specialized function of multiple cell lineages. These functions are critical in lung homeostatic processes including cellular migration and proliferation during morphogenesis or in response to repair. Alterations in lung ECMs that expose cells to new cryptic fragments, generated in response to endogenous proteinases or exogenous toxins, are associated with the development of several common respiratory diseases. How lung ECMs provide or relay vital signals to epithelial and mesenchymal cells has shed new light on development and progression of several common chronic respiratory diseases. This review will consider how ECMs regulate lung homeostasis and their reorganization under pathological conditions that can modulate the inflammatory diseases asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Better understanding of changes in the distribution of lung ECM could provide novel therapeutic approaches to treat chronic lung diseases.

IL‐33 induces production of autoantibody against autologous respiratory epithelial cells: a potential mechanism for the pathogenesis of COPD

“…23,36 Concomitantly it is accepted that endogenous fragments from damaged airways epithelium and even lung extracellular matrix proteins, when 'exposed' by injury, may become self-determinants serving as new autoimmune epitopes. 37 Our data clearly imply, however, that over-production of IL-33 or lung tissue damage alone are insufficient to induce lung inflammation and autoantibody production in the experimental mice, and that it is the coincidence of these that triggers an autoimmune response putatively relevant to the pathogenesis of COPD. Clearly, the precise role of IL-33 in this process, for example as an adjuvant or to overcome immune tolerance of self-antigens, remains to be explored.…”

“…IL‐33 is known to be produced principally by alveolar type II epithelial cells, and is rapidly released following activation or damage of the cells by viruses, allergens and other environmental insults impacting on the airways . Concomitantly it is accepted that endogenous fragments from damaged airways epithelium and even lung extracellular matrix proteins, when ‘exposed’ by injury, may become self‐determinants serving as new autoimmune epitopes . Our data clearly imply, however, that over‐production of IL‐33 or lung tissue damage alone are insufficient to induce lung inflammation and autoantibody production in the experimental mice, and that it is the coincidence of these that triggers an autoimmune response putatively relevant to the pathogenesis of COPD.…”

NETest Liquid Biopsy Is Diagnostic of Lung Neuroendocrine Tumors and Identifies Progressive Disease

“…A similar process has been described in chronic gastritis with increased ECL cell proliferation and concomitant increases in neuroendocrine gene expression [42]. Since inflammation is a common correlative phenomenon associated with both chronic obstructive pulmonary disease and IPF [43, 44], we evaluated whether idiopathic fibrotic changes in the lung might also elevate the NETest. The NETest was positive in 36% of IPF patients, but levels were not significantly increased ( p = 0.23) versus controls.…”

β1 Integrin regulates adult lung alveolar epithelial cell inflammation

“…Integrins are heterodimeric transmembrane receptors consisting of α and β subunits that bind extracellular matrix (ECM) components; propagate bidirectional signaling (1)(2)(3)(4)(5); and regulate critical processes such as adhesion, migration and proliferation that are required for the development of multicellular organisms (6)(7)(8)(9)(10). Of the 24 known α-β integrin heterodimers, 12 integrins contain the β 1 subunit.…”