Crosstalk of Airway Smooth Muscle and Epithelial Cells in Chronic Lung Diseases

Abstract

Chronic pulmonary diseases such as asthma, COPD, and Idiopathic pulmonary fibrosis are significant causes of mortality and morbidity worldwide. Currently, there is no radical treatment for many chronic pulmonary diseases, and the treatment options focus on relieving the symptoms and improving lung function. Therefore, efficient therapeutic agents are highly needed. Bronchial epithelial cells and airway smooth muscle cells and their crosstalk play a significant role in the pathogenesis of these diseases. Thus, targeting the interactions of these two cell types could open the door to a new generation of effective therapeutic options. However, the studies on how these two cell types interact and how their crosstalk adds up to respiratory diseases are not well established. With the rise of modern research tools and technology, such as lab-on-chip, organoids, co-culture techniques, and advanced immunofluorescence imaging, a substantial degree of evidence about these cell interactions emerged. Hence, this contribution aims to review the growing evidence of bronchial epithelial cells and airway smooth muscle cells crosstalk under normal and pathophysiological conditions. The review first deliberates the effects of both healthy and stressed epithelial cells on airway smooth muscle cells, taking into account three themes; contraction, migration, and proliferation. Then, it discusses the impact of airway smooth muscle cells on the epithelium in inflammatory settings. Later, it examines the role of airway smooth muscle cells in the early development of bronchial epithelial cells and their recovery after injury.

Airway epithelial cells promote in vitro airway smooth muscle cell proliferation by activating the Wnt/β-catenin pathway.

“…Over the years, numerous researchers have studied the interaction between AECs (airway epithelial cells) and ASMCs (airway smooth muscle cells). 23 AECs can alter the contractile properties of ASMCs, enhancing their contractility. Under mechanical compression, epithelial cells exhibit an increased capacity to potentiate the contractility of smooth muscle cells.…”

“…22 However, the mechanism by which epithelial cells can promote the proliferation of smooth muscle cells has not been elucidated., 21 the exact mechanisms of this in uence and the resultant alterations in smooth muscle cells have not been clearly delineated. 6,23 The proliferation of airway smooth muscle is controlled by multiple pathways including the activation of the ERK pathway and the PI3K pathway. 24 The Wnt/β-catenin signaling pathway is a conserved pathway that plays a signi cant role in cell proliferation, migration, apoptosis, polarity and morphogenesis.…”

Autophagy/Mitophagy in Airway Diseases: Impact of Oxidative Stress on Epithelial Cells

“…The basal cells are strongly attached to a basement membrane and to each other through tight junctions (TJs) and adherens junctions (AJs), which contribute to epithelial regeneration following injury. Under the basal membrane there is the lamina propria, covered by bands of airway smooth muscle cells, and formed by an extracellular matrix (ECM) mixture containing a variety of immune cells and fibroblasts [ 65 , 66 ].…”