Centre for Heart Lung Innovation, St. Paul's Hospital, Vancouver, BC V6Z 1Y6, Canada.
Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC V5X 1M9, Canada.
Cells. 2021 Jul 6;10(7):1706. doi: 10.3390/cells10071706.
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.
肺细胞外基质（ECM）在肺的正常结构中起着关键作用，从胚胎肺发育到呼吸成人肺的机械稳定性和弹性回弹。肺 ECM 可以通过 ECM 硬度、孔隙率、形貌和不溶性来调节细胞的生物物理环境。在相互作用中，肺 ECM 的动态是由周围的结构和免疫细胞合成、降解和组织 ECM 成分的结果。反复的肺损伤和修复会引发异常 ECM 蛋白沉积的恶性循环，同时伴随着 ECM 硬度的升高，这对细胞和组织功能有持久的影响。控制损伤修复的过程受到几种途径的调节；然而，在哮喘、慢性阻塞性肺疾病（COPD）和特发性肺纤维化（IPF）等慢性肺部疾病中，这些过程受到损害，导致细胞功能受损和 ECM 重塑。目前的估计表明，超过 60%的人类编码转录本受 miRNAs 调节。miRNAs 是一种小的非编码 RNA，可调节基因表达并调节细胞功能。本综述重点介绍了 miRNAs 调节细胞 ECM 合成、降解和形貌的最新知识，以及它们在哮喘、COPD 和 IPF 中的失调。
