Abstract：
Typically, airway remodeling caused by migration and proliferation of airway smooth muscle cells (ASMCs) plays a crucial role in the pathophysiological characteristics of asthma development. Cystatin 1 (CST1), a protein-coding gene referred to as Cystatin SN, is highly expressed in asthma patients. However, the role of CST1 and related molecular mechanisms in the development of asthma remains to be explored. This study aims to investigate the role of CST1 in asthma progression and present related molecular mechanisms. To explore these aspects, human ASMCs with platelet-derived growth factor BB (PDGF-BB) are initially stimulated and applied as a cellular model of asthma. Further, CST1 is knocked down with small interfering ribose nucleic acid (siRNA) overexpressed with plasmids. Then, 5-ethynyl-2\'-deoxyuridine (EdU) and Cell Count Kit (CCK)-8 assays are applied to assess the cell proliferation rates. Further, Transwell and Western blot analyses for migration of cells and expression of MMP1 and MMP9 proteins are assessed, respectively. Under PDGF-BB stimulation, human ASMCs showed an increased CST1 expression, enhanced proliferation, and migration abilities, as well as up-regulated PI3K/AKT signaling pathway. Further, knockdown or overexpression of CST1 presented the declined or enhanced proliferation, migration, and up-regulation of the PI3K/AKT signaling pathway of human ASMCs. Inhibiting PI3K/AKT signaling pathway displayed the reduced migration and proliferation of human ASMCs. In summary, these findings indicated that CST1 played an essential role in the progression of asthma by activating the PI3K/AKT signaling pathway and promoting the migration and proliferation abilities of human ASMCs treated with PDGF-BB.
摘要：
通常,气道平滑肌细胞（ASMCs）的迁移和增殖引起的气道重塑在哮喘发生发展的病理生理特征中起着至关重要的作用。胱抑素1（CST1），一种称为胱抑素SN的蛋白质编码基因，在哮喘患者中高表达。然而,CST1及其相关分子机制在哮喘发生发展中的作用有待进一步探讨。本研究旨在探讨CST1在哮喘进展中的作用及相关分子机制。为了探索这些方面，含有血小板衍生生长因子BB(PDGF-BB)的人ASMC最初被刺激并用作哮喘的细胞模型。Further,用质粒过表达的小干扰核糖核酸(siRNA)敲低CST1。然后，应用5-乙炔基-2'-脱氧尿苷(EdU)和细胞计数试剂盒(CCK)-8测定来评估细胞增殖速率。Further,评估细胞迁移和MMP1和MMP9蛋白表达的Transwell和Western印迹分析。分别。在PDGF-BB刺激下，人类ASMC显示CST1表达增加，增强扩散，和迁移能力，以及上调PI3K/AKT信号通路。Further,CST1的敲低或过表达呈现减少或增强的增殖，迁移,以及人ASMCPI3K/AKT信号通路的上调。抑制PI3K/AKT信号通路显示人ASMC的迁移和增殖减少。总之,这些结果表明,CST1通过激活PI3K/AKT信号通路并促进PDGF-BB治疗的人ASMC的迁移和增殖能力,在哮喘的进展中发挥了重要作用.
