Increased deposition of glycosaminoglycans and altered structure of heparan sulfate in idiopathic pulmonary fibrosis. (February 2017)

• Record Type: Journal Article
• Authors: Westergren-Thorsson, Gunilla; Hedström, Ulf; Nybom, Annika; Tykesson, Emil; Åhrman, Emma; Hornfelt, Marie; Maccarana, Marco; van Kuppevelt, Toin H.; Dellgren, Göran; Wildt, Marie; Zhou, Xiao-Hong; Eriksson, Leif; Bjermer, Leif; Hallgren, Oskar
• Is Part Of: International journal of biochemistry & cell biology. Volume 83(2017)
• Page Start: 27
• Page End: 38
• Publication Date: 2017-02
• Subjects: IPF idiopathic pulmonary fibrosis -- ECM extracellular matrix -- GAG glycosaminoglycan -- HS heparan sulfate -- CS chondroitin sulfate -- DS dermatan sulfate -- HA hyaluronan -- UA uronic acid -- GlcA glucuronic acid -- IdoA iduronic acid -- GalNAc N-acetyl-d-galactosamine -- GlcNAc N-acetyl glucosamine -- FGF fibroblast growth factor -- VEGF vascular endothelial growth factor -- PDGF platelet-derived growth factor -- TGF-beta tumour growth factor-beta -- FBS fetal bovine serum -- AMAC 2-aminoacridone -- BSA bovine serum albumin -- FEV1 forced expiratory volume in 1 s -- FVC forced vital capacity -- TLC total lung capacity -- DLCO diffusion capacity for carbon monoxide -- RP-HPLC reversed-phase high pressure liquid chromatography -- MS mass spectrometry -- qPCR quantitative polymerase chain reaction; Idiopathic pulmonary fibrosis -- Heparan sulfate -- Chondroitin sulfate -- Glycosaminoglycan -- Collagen; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2016.12.005
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: 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.