Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung

Abstract

Mechanical stress plays a critical role among development, functional maturation, and pathogenesis of pulmonary tissues, especially for the alveolar epithelial cells and vascular endothelial cells located in the microenvironment established with vascular network and bronchial-alveolar network. Alveolar epithelial cells are mainly loaded by cyclic strain and air pressure tension. While vascular endothelial cells are exposed to shear stress and cyclic strain. Currently, the emerging evidences demonstrated that non-physiological mechanical forces would lead to several pulmonary diseases, including pulmonary hypertension, fibrosis, and ventilation induced lung injury. Furthermore, a series of intracellular signaling had been identified to be involved in mechanotransduction and participated in regulating the physiological homeostasis and pathophysiological process. Besides, the communications between alveolar epithelium and vascular endothelium under non-physiological stress contribute to the remodeling of the pulmonary micro-environment in collaboration, including hypoxia induced injuries, endothelial permeability impairment, extracellular matrix stiffness elevation, metabolic alternation, and inflammation activation. In this review, we aim to summarize the current understandings of mechanotransduction on the relation between mechanical forces acting on the lung and biological response in mechanical overloading related diseases. We also would like to emphasize the interplays between alveolar epithelium and vascular endothelium, providing new insights into pulmonary diseases pathogenesis, and potential targets for therapy.

Extracellular vesicles in the pathogenesis and treatment of acute lung injury

“…The lung air-blood barrier, which includes the alveolar epithelial and vascular endothelial barriers, performs several vital functions by maintaining alveolar structure and the balance of alveolar fluid clearance and material exchange [ 33 ]. But under non-physiological stress conditions, mechanical transduction between AECs and vascular endothelial can regulate pathophysiological process [ 34 ]. AECs experience mechanical strain during normal breathing which results in different stresses at their apical and basolateral surfaces [ 35 ].…”

Pathogenic Mechanisms of Pulmonary Arterial Hypertension

“… 39 In patients with pulmonary fibrosis complicated with PAH, PAH promotes the progression of pulmonary fibrosis by exposing capillary ECs to higher mechanical stress. 40 …”

Attenuation of Ventilation-Enhanced Epithelial–Mesenchymal Transition through the Phosphoinositide 3-Kinase-γ in a Murine Bleomycin-Induced Acute Lung Injury Model

“…Mechanical ventilation (MV) is often used to maintain life in patients with ARDS. However, despite the widespread use of lung-protective ventilation strategies, ventilator-induced lung injury (VILI), which is characterized by an initial inhomogeneous inflammatory reaction or epithelial injury followed by a fibroproliferative phase with extracellular matrix (ECM) accumulation, continues to occur [ 1 , 2 , 3 , 4 ].…”

“…The three major factors that drive the differentiation of fibroblasts to myofibroblasts are high tidal volume mechanical stress, local increase in transforming growth factor-β1 (TGF-β1), and the presence of the extra domain A splice variant of fibronectin [ 1 , 2 ]. The lesional effect of MV on the ECM may be influenced by the following factors: increased transpulmonary pressure, heterogeneous distribution of ventilation, increased tissue stretch, and decreased pulmonary lymphatic drainage [ 1 , 4 , 5 ]. However, the conditions that determine alveolar recovery and fibrosis remain unclear.…”