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.CONCLUSION: 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Nyckelord

Adult

Aged

Aged, 80 and over

Biopsy

Cells, Cultured

Chondroitin Sulfate Proteoglycans

Chromatography, Gel

Connective Tissue

Dermatan Sulfate

Female

Fibroblasts

Humans

Male

Middle Aged

Proteoglycans

RNA, Messenger

Scleroderma, Systemic

Journal Article

Research Support, Non-U.S. Gov't

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)