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静息状态下哮喘和非哮喘气道平滑肌细胞分泌的细胞外基质对血管生成的调节作用相似。

Angiogenic regulatory influence of extracellular matrix deposited by resting state asthmatic and non-asthmatic airway smooth muscle cells is similar.

作者信息

Faiz Alen, Harkness Louise M, Tjin Gavin, Bernal Victor, Horvatovich Peter, James Alan, Elliot John G, Burgess Janette K, Ashton Anthony W

机构信息

Respiratory Cellular and Molecular Biology, Woolcock Institute of Medical Research. Sydney, NSW, Australia.

Emphysema Center, Woolcock Institute of Medical Research, The University of Sydney, Glebe, NSW, Australia.

出版信息

J Cell Mol Med. 2021 Jul;25(13):6438-6447. doi: 10.1111/jcmm.16648. Epub 2021 Jun 18.

Abstract

The extracellular matrix (ECM) is the tissue microenvironment that regulates the characteristics of stromal and systemic cells to control processes such as inflammation and angiogenesis. Despite ongoing anti-inflammatory treatment, low levels of inflammation exist in the airways in asthma, which alters ECM deposition by airway smooth muscle (ASM) cells. The altered ECM causes aberrant behaviour of cells, such as endothelial cells, in the airway tissue. We therefore sought to characterize the composition and angiogenic potential of the ECM deposited by asthmatic and non-asthmatic ASM. After 72 hours under non-stimulated conditions, the ECM deposited by primary human asthmatic ASM cells was equal in total protein, collagen I, III and fibronectin content to that from non-asthmatic ASM cells. Further, the matrices of non-asthmatic and asthmatic ASM cells were equivalent in regulating the growth, activity, attachment and migration of primary human umbilical vein endothelial cells (HUVECs). Under basal conditions, asthmatic and non-asthmatic ASM cells intrinsically deposit an ECM of equivalent composition and angiogenic potential. Previous findings indicate that dysregulation of the airway ECM is driven even by low levels of inflammatory provocation. This study suggests the need for more effective anti-inflammatory therapies in asthma to maintain the airway ECM and regulate ECM-mediated aberrant angiogenesis.

摘要

细胞外基质(ECM)是一种组织微环境,可调节基质细胞和全身细胞的特性,以控制炎症和血管生成等过程。尽管进行了持续的抗炎治疗,但哮喘患者气道中仍存在低水平的炎症,这会改变气道平滑肌(ASM)细胞的ECM沉积。改变的ECM会导致气道组织中细胞(如内皮细胞)的异常行为。因此,我们试图表征哮喘和非哮喘ASM沉积的ECM的组成和血管生成潜力。在非刺激条件下培养72小时后,原代人哮喘ASM细胞沉积的ECM在总蛋白、I型胶原、III型胶原和纤连蛋白含量方面与非哮喘ASM细胞沉积的ECM相当。此外,非哮喘和哮喘ASM细胞的基质在调节原代人脐静脉内皮细胞(HUVECs)的生长、活性、黏附和迁移方面是等效的。在基础条件下,哮喘和非哮喘ASM细胞内在地沉积具有等效组成和血管生成潜力的ECM。先前的研究结果表明,即使是低水平的炎症刺激也会导致气道ECM失调。这项研究表明,在哮喘中需要更有效的抗炎疗法来维持气道ECM并调节ECM介导的异常血管生成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/86a2/8256353/be74fdf84df6/JCMM-25-6438-g004.jpg

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