Glycan profiling of a defect in decorin glycosylation in equine systemic proteoglycan accumulation, a potential model of progeroid form of Ehlers-Danlos syndrome.
Abstract: Defects in glycosylation of decorin can result in systemic hereditary disease. A mutation in the galactosyl transferase I gene is the underlying defect of a progeroid form of Ehlers-Danlos syndrome. We have previously described pathological changes in equine systemic proteoglycan accumulation (ESPA, formerly degenerative suspensory ligament desmitis) as consisting of excessive presence of decorin and other proteoglycans in organs and structures with a high content of connective tissue. Using liquid chromatography/mass spectrometry, and one- and two-dimensional immunoblotting we have determined that decorin from ESPA-tendons had a higher molecular weight than decorin from non-affected control tendons. Glycosaminoglycan structure and monosaccharide composition were determined with HPLC analysis of chondroitinase ABC-digested glycosaminoglycans and gas chromatography/mass spectrometry. This analysis revealed an increase in the total content of sulfated disaccharides, particularly due to enhanced sulfation at 6-position of N-acetyl galactosamine (GalNAc) with a subsequent decrease in the ratio of 4-sulfation to 6-sulfation disaccharides in the ESPA decorin. The ESPA-affected decorin also exhibited altered biological activity resulting in (1) diminished binding of TGFbeta1 (and of anti-decorin antibody) to ESPA decorin, and (2) increased expression of TGFbeta1 in ESPA tissues.
Copyright 2010 Elsevier Inc. All rights reserved.
Publication Date: 2010-06-17 PubMed ID: 20599673DOI: 10.1016/j.abb.2010.06.017Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research article focuses on studying how defects in the glycosylation of a protein called decorin can lead to systemic hereditary disease, particularly a type of Ehlers-Danlos syndrome, utilizing an equine model. The study reveals that the affected decorin in the equine model has a higher molecular weight and exhibits altered biological activity.
Understanding Glycosylation and Decorin
- The research article discusses defects in a process called glycosylation, which attaches glycans (sugar molecules) to proteins or lipids, effectively altering their function. This is performed on a protein called decorin, a protein that plays a crucial role in connective tissue and organ function.
- Problems with decorin glycosylation can lead to systemic hereditary diseases, in this case, a progeroid form of Ehlers-Danlos syndrome, a group of disorders affecting connective tissues and characterized by unusually flexible joints and stretchy skin.
Research on Equine Model
- The researchers used an equine model of a condition called equine systemic proteoglycan accumulation (ESPA) for their study. ESPA is marked by an excessive amount of decorin and other proteoglycans in tissues and structures with a significant amount of connective tissue, such as tendons.
- They found that decorin derived from ESPA-affected tendons had a higher molecular weight than decorin from unaffected tendons, indicating a change in its composition.
Glycosaminoglycan Structure and Composition
- The structure and composition of glycosaminoglycans, a type of complex carbohydrate attached to decorin, were studied using HPLC analysis and gas chromatography/mass spectrometry.
- Results showed an increase in total content of sulfated disaccharides, due to enhanced sulfation at the 6-position of a monosaccharide called N-acetyl galactosamine (GalNAc). This alteration caused a subsequent decrease in the ratio of 4-sulfation to 6-sulfation disaccharides in ESPA decorin.
Altered Biological Activity of Decorin
- The altered glycosylation of decorin in ESPA also led to varied biological outcomes, specifically diminished binding of a growth factor (TGFbeta1) and increased expression of this same growth factor in ESPA tissues.
Cite This Article
APA
Kim B, Yoon JH, Zhang J, Eric Mueller PO, Halper J.
(2010).
Glycan profiling of a defect in decorin glycosylation in equine systemic proteoglycan accumulation, a potential model of progeroid form of Ehlers-Danlos syndrome.
Arch Biochem Biophys, 501(2), 221-231.
https://doi.org/10.1016/j.abb.2010.06.017 Publication
Researcher Affiliations
- Department of Pathology, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602, USA.
MeSH Terms
- Animals
- Base Sequence
- DNA Primers / genetics
- Decorin
- Disease Models, Animal
- Ehlers-Danlos Syndrome / genetics
- Ehlers-Danlos Syndrome / metabolism
- Ehlers-Danlos Syndrome / pathology
- Extracellular Matrix Proteins / chemistry
- Extracellular Matrix Proteins / metabolism
- Female
- Glycosylation
- Horse Diseases / genetics
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Humans
- Male
- Polysaccharides / chemistry
- Progeria / genetics
- Progeria / metabolism
- Progeria / pathology
- Proteoglycans / chemistry
- Proteoglycans / metabolism
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Tendons / metabolism
- Transforming Growth Factor beta1 / genetics
- Transforming Growth Factor beta1 / metabolism
Citations
This article has been cited 14 times.- Momen M, Brauer K, Patterson MM, Sample SJ, Binversie EE, Davis BW, Cothran EG, Rosa GJM, Brounts SH, Muir P. Genetic architecture and polygenic risk score prediction of degenerative suspensory ligament desmitis (DSLD) in the Peruvian Horse. Front Genet 2023;14:1201628.
- Roberts JH, Zhang J, David F, McLean A, Blumenshine K, Müller-Alander E, Halper J. Expression of genes with biomarker potential identified in skin from DSLD-affected horses increases with age. PLoS One 2023;18(7):e0287740.
- Roberts JH, Halper J. Connective Tissue Disorders in Domestic Animals. Adv Exp Med Biol 2021;1348:325-335.
- Haythorn A, Young M, Stanton J, Zhang J, Mueller POE, Halper J. Differential gene expression in skin RNA of horses affected with degenerative suspensory ligament desmitis. J Orthop Surg Res 2020 Oct 7;15(1):460.
- Gains CC, Correia JC, Baan GC, Noort W, Screen HRC, Maas H. Force Transmission Between the Gastrocnemius and Soleus Sub-Tendons of the Achilles Tendon in Rat. Front Bioeng Biotechnol 2020;8:700.
- Kram V, Shainer R, Jani P, Meester JAN, Loeys B, Young MF. Biglycan in the Skeleton. J Histochem Cytochem 2020 Nov;68(11):747-762.
- Zappia J, Joiret M, Sanchez C, Lambert C, Geris L, Muller M, Henrotin Y. From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues. Biomolecules 2020 Jan 3;10(1).
- Young M, Moshood O, Zhang J, Sarbacher CA, Mueller POE, Halper J. Does BMP2 play a role in the pathogenesis of equine degenerative suspensory ligament desmitis?. BMC Res Notes 2018 Sep 18;11(1):672.
- Luo W, Sandy J, Trella K, Gorski D, Gao S, Li J, Brounts S, Galante J, Plaas A. Degenerative Suspensory Ligament Desmitis (DSLD) in Peruvian Paso Horses Is Characterized by Altered Expression of TGFβ Signaling Components in Adipose-Derived Stromal Fibroblasts. PLoS One 2016;11(11):e0167069.
- Thorpe CT, Karunaseelan KJ, Ng Chieng Hin J, Riley GP, Birch HL, Clegg PD, Screen HR. Distribution of proteins within different compartments of tendon varies according to tendon type. J Anat 2016 Sep;229(3):450-8.
- Thorpe CT, Peffers MJ, Simpson D, Halliwell E, Screen HR, Clegg PD. Anatomical heterogeneity of tendon: Fascicular and interfascicular tendon compartments have distinct proteomic composition. Sci Rep 2016 Feb 4;6:20455.
- Sejersen MH, Frost P, Hansen TB, Deutch SR, Svendsen SW. Proteomics perspectives in rotator cuff research: a systematic review of gene expression and protein composition in human tendinopathy. PLoS One 2015;10(4):e0119974.
- Thorpe CT, Birch HL, Clegg PD, Screen HR. The role of the non-collagenous matrix in tendon function. Int J Exp Pathol 2013 Aug;94(4):248-59.
- Guest DJ, Birch HL, Thorpe CT. A review of the equine suspensory ligament: Injury prone yet understudied. Equine Vet J 2025 Sep;57(5):1167-1182.
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