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Analysis of the structure and neuritogenic activity of chondroitin sulfate/dermatan sulfate hybrid chains from porcine fetal membranes

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Abstract

The amniotic membrane (AM) is the innermost layer of fetal membranes and possesses various biological activities. Although the mechanism underlying these biological activities remains unclear, unique components seem to be involved. AM contains various extracellular matrix components such as type I collagen, laminin, fibronectin, hyaluronan, and proteoglycans bearing chondroitin sulfate/dermatan sulfate (CS/DS) glycosaminoglycan side chains. Since CS/DS have been implicated in various biological processes, we hypothesized that CS/DS in AM may play a major role in the biological activities of AM. Therefore, the structure and bioactivity of the CS/DS chains from porcine fetal membranes (FM-CS/DS) were investigated. A compositional analysis using various chondroitinases revealed that the characteristic DS domain comprised of iduronic acid-containing disaccharide units is embedded in FM-CS/DS, along with predominant disaccharide units, GlcA-GalNAc, GlcA-GalNAc(4-O-sulfate), and GlcA-GalNAc(6-O-sulfate), where GlcA and GalNAc represent D-glucuronic acid and N-acetyl-D-galactosamine, respectively. The average molecular mass of FM-CS/DS chains was unusually large and estimated to be 250 – 300 kDa. The FM-CS/DS chains showed neurite outgrowth-promoting activity, which was eliminated by digestion with chondroitinase ABC of the CS/DS chains. This activity was suppressed by antibodies against growth factors including pleiotrophin, midkine, and fibroblast growth factor-2, suggesting the involvement of these growth factors in the neurite outgrowth-promoting activity. The binding of these growth factors to FM-CS/DS was also demonstrated by surface plasmon resonance spectroscopy.

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Abbreviations

GAG:

glycosaminoglycan

CS:

chondroitin sulfate

DS:

dermatan sulfate

HS:

heparan sulfate

KS:

keratan sulfate

HA:

hyaluronan

AM:

amniotic membrane

FM:

fetal membrane

IdoA:

L-iduronic acid

GlcA:

D-glucuronic acid

GalNAc:

N-acetyl-D-galactosamine

FGF-2:

fibroblast growth factor-2

PTN:

pleiotrophin

MK:

midkine

HGF:

hepatocyte growth factor

P-ORN:

poly-DL-ornithine

HPLC:

high performance liquid chromatography

CSase:

chondroitinase

NOP:

neurite outgrowth-promoting

2AB:

2-aminobenzamide

∆HexA:

4-deoxy-L-threo-hex-4-enepyranosyluronic acid

IU:

international units

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Acknowledgements

This work was supported by Grant-in-aid for Scientific Research (B) 20390019 (to K. S.) from MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan), and Sapporo Biocluster “Bio-S”, the Knowledge Cluster Initiative of the MEXT.

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Authors and Affiliations

  1. Laboratory of Proteoglycan Signaling and Therapeutics, Graduate School of Life Science, Hokkaido University, Frontier Research Center for Post-Genomic Science and Technology, Nishi 11-choume, Kita 21-jo, Kita-ku, Sapporo, Hokkaido, 001-0021, Japan

    Taishi Hashiguchi, Shuji Mizumoto, Shuhei Yamada & Kazuyuki Sugahara

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  1. Taishi Hashiguchi
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  2. Shuji Mizumoto
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  3. Shuhei Yamada
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Correspondence to Shuhei Yamada or Kazuyuki Sugahara.

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Hashiguchi, T., Mizumoto, S., Yamada, S. et al. Analysis of the structure and neuritogenic activity of chondroitin sulfate/dermatan sulfate hybrid chains from porcine fetal membranes. Glycoconj J 27, 49–60 (2010). https://doi.org/10.1007/s10719-009-9253-x

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