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Elevated matrix metalloproteinase-9 in patients with systemic sclerosis.
Wan-Uk Kim1, So-Youn Min, Mi-La Cho
1Division of Rheumatology, Department of Internal Medicine, Catholic Research Institutes of Medical Science, School of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. wan725@catholic.ac.kr
Arthritis Research & Therapy
|January 12, 2005
Summary
Matrix metalloproteinase-9 (MMP-9) is elevated in systemic sclerosis (SSc) patients, correlating with skin scores. Increased MMP-9 from dermal fibroblasts may drive fibrotic remodeling in SSc.
Area of Science:
- Biochemistry
- Immunology
- Dermatology
Background:
- Matrix metalloproteinase-9 (MMP-9) is linked to fibrosis in various diseases.
- Systemic sclerosis (SSc) is a fibrotic autoimmune condition with unclear pathogenesis.
- Investigating MMP-9 in SSc may reveal therapeutic targets.
Purpose of the Study:
- To examine MMP-9 expression and its clinical significance in systemic sclerosis (SSc).
- To determine if MMP-9 levels correlate with disease severity and specific SSc subtypes.
- To investigate the source of elevated MMP-9 in SSc patients.
Main Methods:
- Serum samples from SSc patients (n=42) and healthy controls (n=32) were analyzed for MMP-9 and TIMP-1 concentrations.
- MMP-9 levels were compared between diffuse and limited SSc subtypes.
- Correlations between serum MMP-9 and clinical parameters (Rodnan score, TGF-β) were assessed.
- Dermal fibroblasts from SSc patients and controls were stimulated with cytokines (IL-1β, TNF-α, TGF-β) to measure MMP-9 production.
- The effect of cyclosporin A on MMP-9 production was evaluated.
Main Results:
- SSc patients exhibited higher serum MMP-9 and TIMP-1 concentrations and a higher MMP-9/TIMP-1 ratio compared to controls.
- Serum MMP-9 levels were significantly elevated in the diffuse SSc subtype compared to the limited subtype.
- Serum MMP-9 concentrations positively correlated with the Rodnan skin score and serum TGF-β levels.
- SSc dermal fibroblasts produced more MMP-9 than control fibroblasts upon cytokine stimulation.
- Cyclosporin A partially inhibited the increased MMP-9 production by SSc fibroblasts.
Conclusions:
- Elevated serum MMP-9 concentrations are characteristic of systemic sclerosis.
- Increased MMP-9 levels in SSc correlate with disease severity, particularly skin involvement.
- Dermal fibroblasts are a likely source of elevated MMP-9 in SSc, potentially contributing to fibrotic processes.
- MMP-9 represents a potential therapeutic target for managing fibrotic remodeling in SSc.