Abstract
The lung extracellular matrix (ECM) plays a key role in the normal architecture of the lung, from embryonic lung development to mechanical stability and elastic recoil of the breathing adult lung. The lung ECM can modulate the biophysical environment of cells through ECM stiffness, porosity, topography and insolubility. In a reciprocal interaction, lung ECM dynamics result from the synthesis, degradation and organization of ECM components by the surrounding structural and immune cells. Repeated lung injury and repair can trigger a vicious cycle of aberrant ECM protein deposition, accompanied by elevated ECM stiffness, which has a lasting effect on cell and tissue function. The processes governing the resolution of injury repair are regulated by several pathways; however, in chronic lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary disease (IPF) these processes are compromised, resulting in impaired cell function and ECM remodeling. Current estimates show that more than 60% of the human coding transcripts are regulated by miRNAs. miRNAs are small non-coding RNAs that regulate gene expressions and modulate cellular functions. This review is focused on the current knowledge of miRNAs in regulating ECM synthesis, degradation and topography by cells and their dysregulation in asthma, COPD and IPF.
Highlights
The objective of this review is to evaluate the current knowledge on the regulation of the lung extracellular matrix (ECM) in health and disease by cells through the epigenetic regulation by miRNAs
The processes governing the resolution of injury repair are regulated by several pathways, in chronic fibrotic lung diseases the processes are compromised, resulting in impaired fibroblast proliferation, apoptosis and aberrant ECM remodelling [3,76]. Disruption of this balance changes the dynamics of the lung ECM with characteristics such as stiffness and elastance, as seen in asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) [78–80]
Emerging evidence suggests that the ATP binding cassette (ABC) transporter family of proteins that is involved in drug resistance is regulated by miRNAs, and this provides a potential mechanism for the use of miRNAs in drug resistance [178]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The lung ECM provides both biochemical and biophysical cues, which direct cellular functions and differentiation. The lung ECM can alter the biochemical environment of surrounding cells, by storing and sequestering growth factors and cytokines to regulate spatially and temporally their bioavailability. The lung ECM can modulate the biophysical environment of cells through. ECM stiffness, porosity, topography (spatial arrangement and orientation) and insolubility. Lung ECM molecules connect to cells via integrins, syndecans and other receptors to influence cell signalling, migration and proliferation. The lung ECM is remodelled by cells, whereby its components are deposited, degraded or modified in a reciprocal relationship [3,4]. The objective of this review is to evaluate the current knowledge on the regulation of the lung ECM in health and disease by cells through the epigenetic regulation by miRNAs
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