Friday, July 02, 2010


Link to latest research on right under "Articles."

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 TGFβ1 (and of anti-decorin antibody) to ESPA decorin, and (2) increased expression of TGFβ1 in ESPA tissues.
In conclusion, we have identified several novel processes that may contribute to the pathogenesis of ESPA. We hypothesize that decorin undergoes changes in glycosylation of its glycosaminoglycans chains. Future experiments will demonstrate whether these changes are due to genetic changes in one or more of the glycosylation enzymes. We hypothesize that the decreased affinity of the proteoglycan for TGFβ1 leads to changes in TGFb expression and has a direct effect on collagen and proteoglycan activity. Future studies will target the effect of these perturbations in glycosylation on fibrillogenesis and impaired biomechanical function.


Pathogenesis -- is the origination and development of a disease
Decorin is a proteoglycan
Glycosylation -- is the enzymatic process that links saccharides to produce glycans attached to proteins, ...
Proteoglycan -- a group of polysaccharide-protein joined together and present in connective tissue and cartilage
Fibrillogenesis -- the development of fine fibrils normally present in collagen fibers of connective tissue
TGFβ1 -- Transforming growth factor beta 1 or TGFβ1 is a polypeptide member of the transforming growth factor beta superfamily of cytokines.