Proteoglycans maintain lung stability in an elastase-treated mouse model of emphysema.
Proteoglycans maintain lung stability in an elastase-treated mouse model of emphysema.
复制标题
在弹性蛋白酶治疗的肺气肿小鼠模型中，蛋白聚糖维持肺的稳定性。
DOI：
10.1165/rcmb.2013-0179oc
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发表时间：
2014
影响因子：
6.4
通讯作者：
Suki,Béla
中科院分区：
文献类型：
--
作者：
Takahashi,Ayuko;Majumdar,Arnab;Parameswaran,Harikrishnan;Bartolák-Suki,Erzsébet;Suki,Béla
细胞外基质重塑和组织破裂有助于肺气肿的发展。肺组织弹性是由纤维的拉伸刚度和蛋白聚糖的压缩刚度决定的。目前尚不清楚蛋白聚糖重塑如何影响肺气肿的组织稳定性和破坏。本研究的目的是表征重塑蛋白聚糖在肺气肿肺泡稳定性和组织破坏中的作用。在猪胰腺弹性蛋白酶治疗30天后，在不同的强直条件下评估小鼠肺组织刚度和肺泡变形，这些条件会影响蛋白聚糖的刚度。对肺泡壁的蛋白聚糖进行染色和测定。结合纤维和蛋白聚糖的力学特性，开发了肺泡稳定性和破裂计算模型。虽然绝对组织刚度仅为正常人的24%，但肺气肿患者的相对刚度变化和肺泡形状畸变均增加（P< 0.01和P< 0.001）。在肺气肿患者中，单位肺泡壁长度的糖胺聚糖含量更高（P< 0.001），而糖胺聚糖是造成蛋白聚糖硬度的原因。组织中Versican表达增加，decorin表达减少。我们的网络模型预测，当蛋白聚糖刚度增加时，局部由机械力控制的组织恶化率会降低。因此，这个一般的网络模型解释了为什么增加的蛋白多糖沉积保护肺气肿的肺泡壁不破裂。我们的研究结果表明，在人类肺气肿中观察到的蛋白多糖的损失有助于疾病的进展，而促进蛋白多糖在细胞外基质中的沉积的治疗应减缓肺气肿的进展。
Extracellular matrix remodeling and tissue rupture contribute to the progression of emphysema. Lung tissue elasticity is governed by the tensile stiffness of fibers and the compressive stiffness of proteoglycans. It is not known how proteoglycan remodeling affects tissue stability and destruction in emphysema. The objective of this study was to characterize the role of remodeled proteoglycans in alveolar stability and tissue destruction in emphysema. At 30 days after treatment with porcine pancreatic elastase, mouse lung tissue stiffness and alveolar deformation were evaluated under varying tonicity conditions that affect the stiffness of proteoglycans. Proteoglycans were stained and measured in the alveolar walls. Computational models of alveolar stability and rupture incorporating the mechanical properties of fibers and proteoglycans were developed. Although absolute tissue stiffness was only 24% of normal, changes in relative stiffness and alveolar shape distortion due to changes in tonicity were increased in emphysema (P< 0.01 andP< 0.001). Glycosaminoglycan amount per unit alveolar wall length, which is responsible for proteoglycan stiffness, was higher in emphysema (P< 0.001). Versican expression increased in the tissue, but decorin decreased. Our network model predicted that the rate of tissue deterioration locally governed by mechanical forces was reduced when proteoglycan stiffness was increased. Consequently, this general network model explains why increasing proteoglycan deposition protects the alveolar walls from rupture in emphysema. Our results suggest that the loss of proteoglycans observed in human emphysema contributes to disease progression, whereas treatments that promote proteoglycan deposition in the extracellular matrix should slow the progression of emphysema.