The Role of miRNAs in Extracellular Matrix Repair and Chronic Fibrotic Lung Diseases

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.

Urine-derived exosomes from individuals with IPF carry pro-fibrotic cargo

“…In addition, we recognize that subjects with asthma were not age matched to the control or IPF subjects. The decreased expression of miR-34a and -199, fibrotic inducing microRNAs highlight the differences in cargo content between exosomes from various lung diseases supporting future investigations (Usman, Hsieh, & Hackett, 2021;Weidner et al, 2021).…”

Hsa-Mir-320c, Hsa-Mir-200c-3p, and Hsa-Mir-449c-5p as Potential Specific miRNA Biomarkers of COPD: A Pilot Study

“…Deregulation of miRNAs translates into altered expression of molecules and subsequent alteration in the pathways involved. Differences in the expression of miRNAs involved in the remodeling of the extracellular matrix have been reported in several chronic lung diseases [ 36 ], and in particular, an increase has been shown in the levels of miR-15b in lung tissue from COPD patients, which correlates with disease severity [ 37 ], whereas a decrease was observed in miR-145-5p [ 23 ] and miR-181c [ 38 ]. The Hippo signaling pathway is a master regulator of ECM processes in lung development and disease [ 39 ].…”

Role of MicroRNAs in Signaling Pathways Associated with the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Focus on Epithelial-Mesenchymal Transition

“…Until now, it has been demonstrated that human miRNAs listed in public databases represent only a small fraction of the total human miRNA repertoire [ 38 , 40 , 175 ]; therefore, it is necessary to update these studies to improve our understanding about the complex gene expression regulation network in diseases such as IPF. Some studies have estimated that approximately 60% of the human coding transcripts are regulated by miRNAs [ 38 , 125 , 176 ]. Moreover, recent reports indicate that an important number of miRNAs are associated with the TGF-β-dependent Smad and non-Smad dependent signaling pathway, with the EMT activation process, and with the consequent fibroblast activation and myofibroblast differentiation.…”

“…Therefore, the search, analysis, and discussion of new treatment options are necessary. Among these new options are the miRNAs because of their role as regulators of signaling pathways and cell functionality, which suggests that they probably play a role in this pathology [ 124 , 125 ]. The most recent information on dysregulated miRNAs implicated in the pathophysiology of IPF is depicted in the Table 1 .…”