Altered dermatan sulfate proteoglycan synthesis in fibroblast cultures established from skin of patients with systemic sclerosis.
OBJECTIVE
To study whether changes in the properties of skin from patients with systemic sclerosis (SSc) are the result of altered metabolism of dermatan sulfate proteoglycans.


METHODS
Fibroblast cultures were established from skin of healthy controls, and from affected and unaffected skin of patients with SSc. Synthesized proteoglycans were labeled with 3H glucosamine and 35S sulfate. The amount of mRNA of the different dermatan sulfate proteoglycans was determined by hybridization with the corresponding cDNA probes.


RESULTS
A 2-fold increase in secretion of total proteoglycans was found in cell cultures from affected and normal appearing skin from patients with SSc. The production of 2 different dermatan sulfate proteoglycans was increased. Aggrecan/versican increased 4-fold and decorin 2-fold in cultures of affected skin from patients with SSc. The mRNA for decorin increased 3-fold, while the mRNA level for versican increased only slightly. Similar but less marked changes were noted in cultures from normal appearing skin. In contrast, the biglycan mRNA level decreased and the product could only be found in very small amounts in SSc cultures.


CONCLUSIONS
This marked alteration of dermatan sulfate proteoglycan metabolism distinguishes not only affected skin but also normal appearing SSc skin from that of controls. The altered proteoglycan production may affect organization of matrix fibers and thereby the fibrotic process observed in patients with SSc.
Westergren-Thorsson
G
G
Department of Rheumatology, Lund University, Sweden.
Cöster
L
L
Akesson
A
A
Wollheim
F A
FA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis*; D002850:Chromatography, Gel; D003238:Connective Tissue / Q000737:chemistry*; D003871:Dermatan Sulfate / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011509:Proteoglycans / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D012595:Scleroderma, Systemic / Q000378:metabolism*
D011508:Chondroitin Sulfate Proteoglycans; D011509:Proteoglycans; D012333:RNA, Messenger; C032649:dermatan sulfate proteoglycan; D003871:Dermatan Sulfate