Increased deposition of glycosaminoglycans and altered structure of heparan sulfate in idiopathic pulmonary fibrosis
Increased deposition of glycosaminoglycans and altered structure of heparan sulfate in idiopathic pulmonary fibrosis
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DOI：
10.1016/j.biocel.2016.12.005
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发表时间：
2017-02-01
影响因子：
4
通讯作者：
Hallgren, Oskar
中科院分区：
文献类型：
--
作者：
Westergren-Thorsson, Gunilla;Hedstrom, Ulf;Hallgren, Oskar
特发性肺纤维化(IPF)的特征是细胞外基质(ECM)成分的异常沉积，包括糖胺聚糖(GAG)，这些成分可能通过影响生长因子等关键介质而在重塑过程中发挥作用。我们假设IPF中的GAG可能会改变，这有助于创造一个促纤维化的环境。因此，本研究的目的是观察IPF患者和对照组肺组织中硫酸肝素(HS)、硫酸软骨素/皮肤素(CS/DS)和透明质酸(HA)的精细结构。用高效液相色谱法分析重症IPF患者和供体肺标本中的GAG。用免疫组织化学方法对HS进行评估，并以羟脯氨酸含量作为胶原的定量指标。IPF大鼠肺组织中HS、CS/DS和HA总量增加，但总胶原含量无明显变化。研究发现，由于CS/DS中2-O、6-O和N-硫酸盐化的增加以及更高比例的硫酸盐化，HS的总硫酸盐化相对增加。高度硫酸盐化的HS位于血管和呼吸道基底膜中密度较高的区域和外观较正常的肺泡实质之间的交界区，Perlecan免疫阳性，以及肺泡间质中梭形细胞的细胞表面。这些发现首次表明在IPF中糖胺多聚糖的数量和结构都发生了改变。这些变化可能通过改变生长因子的保留和活性，创造一个有利于纤维化的ECM环境，从而有助于IPF的组织重塑。(C)2016年提交人。爱思唯尔有限公司出版。
Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant deposition of extracellular matrix (ECM) constituents, including glycosaminoglycans (GAGs), that may play a role in remodelling processes by influencing critical mediators such as growth factors. We hypothesize that GAGs may be altered in IPF and that this contribute to create a pro-fibrotic environment. The aim of this study was therefore to examine the fine structure of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) in lung samples from IPF patients and from control subjects. GAGs in lung samples from severe IPF patients and donor lungs were analyzed with HPLC. HS was assessed by immunohistochemistry and collagen was quantified as hydroxyproline content. The total amount of HS, CS/DS and HA was increased in IPF lungs but there was no significant difference in the total collagen content. We found a relative increase in total sulfation of HS due to increment of 2-O, 6-O and N-sulfation and a higher proportion of sulfation in CS/DS. Highly sulfated HS was located in the border zone between denser areas and more normal looking alveolar parenchyma in basement membranes of blood vessels and airways, that were immuno-positive for perlecan, as well as on the cell surface of spindle-shaped cells in the alveolar interstitium. These findings show for the first time that both the amount and structure of glycosaminoglycans are altered in IPF. These changes may contribute to the tissue remodelling in IPF by altering growth factor retention and activity, creating a pro-fibrotic ECM landscape. (C) 2016 The Authors. Published by Elsevier Ltd.