Increased deposition of glycosaminoglycans and altered structure of heparan sulfate in idiopathic pulmonary fibrosis

详细信息    查看全文

• 作者：Gunilla Westergren-Thorsson^a ; Ulf Hedströ ; m^a ; ^b ; Annika Nybom^a ; Emil Tykesson^a ; Emma Å ; hrman^a ; Marie Hornfelt^b ; Marco Maccarana^a ; Toin H. van Kuppevelt^c ; Gö ; ran Dellgren^d ; Marie Wildt^a ; Xiao-Hong Zhou^b ; Leif Eriksson^a ; Leif Bjermer^e ; Oskar Hallgren^a ; ^e ; ^{oskar.hallgren@med.lu.se}
• 关键词：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 ; bov
• 刊名：The International Journal of Biochemistry & Cell Biology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：83
• 期：Complete
• 页码：27-38
• 全文大小：4274 K
• 卷排序：83

文摘

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.