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Elevated matrix metalloproteinase-9 in patients with systemic sclerosis.

Kim WU, Min SY, Cho ML, Hong KH, Shin YJ, Park SH, Cho CS - Arthritis Res. Ther. (2004)

Bottom Line: Serum MMP-9 concentrations were significantly higher in the diffuse type (n = 23) than the limited type of SSc (n = 19).The increased MMP-9 concentrations may be attributable to overproduction by dermal fibroblasts in SSc.These findings suggest that the enhanced production of MMP-9 may contribute to fibrogenic remodeling during the progression of skin sclerosis in SSc.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division 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

ABSTRACT
Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of cancer, autoimmune disease, and various pathologic conditions characterized by excessive fibrosis. In this study, we investigated the expression of MMP-9 and its clinical significance in systemic sclerosis (SSc). The patients (n = 42) with SSc had higher concentrations of MMP-9 and of tissue inhibitor of metalloproteinase-1 (TIMP-1) and a higher ratio of MMP-9 to TIMP-1 in sera than healthy controls (n = 32). Serum MMP-9 concentrations were significantly higher in the diffuse type (n = 23) than the limited type of SSc (n = 19). Serum concentrations of MMP-9 correlated well with the degree of skin involvement, as determined by the Rodnan score and with serum concentrations of transforming growth factor beta. Moreover, dermal fibroblasts from patients with SSc produced more MMP-9 than those from healthy controls when they were stimulated with IL-1beta, tumor necrosis factor alpha, or transforming growth factor beta. Such an increase in MMP-9 production was partially blocked by treatment with cyclosporin A. In summary, the serum MMP-9 concentrations were elevated in SSc patients and correlated well with skin scores. The increased MMP-9 concentrations may be attributable to overproduction by dermal fibroblasts in SSc. These findings suggest that the enhanced production of MMP-9 may contribute to fibrogenic remodeling during the progression of skin sclerosis in SSc.

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Gelatinase activity of matrix metalloproteinase (MMP)-2 (72 kDa) and MMP-9 (92 kDa) in sera of patients with systemic sclerosis (SSc) and healthy controls. Sera (0.5 μl) from 20 patients with SSc and 10 healthy controls were analyzed for their MMP-2 and MMP-9 activities by gel zymography. As a positive control, supernatants from cultured HT1080 cell lines (HT) stimulated with 10 μg/ml of concanavalin A were used. Numbers in parentheses are MMP-9 concentrations (ng/ml) determined by ELISA. The figure shows representative results for serum samples from the two groups.
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Figure 3: Gelatinase activity of matrix metalloproteinase (MMP)-2 (72 kDa) and MMP-9 (92 kDa) in sera of patients with systemic sclerosis (SSc) and healthy controls. Sera (0.5 μl) from 20 patients with SSc and 10 healthy controls were analyzed for their MMP-2 and MMP-9 activities by gel zymography. As a positive control, supernatants from cultured HT1080 cell lines (HT) stimulated with 10 μg/ml of concanavalin A were used. Numbers in parentheses are MMP-9 concentrations (ng/ml) determined by ELISA. The figure shows representative results for serum samples from the two groups.

Mentions: We used gel zymography to study sera of 20 SSc patients and 10 healthy controls, all selected unsystematically, to ascertain the serum gelatinase activity of MMP-9. As can be seen in Fig. 3, the 92 kDa band, consistent with the latent form of MMP-9, was detected in the sera of all subjects. The bands in Fig. 3 represent the latent form of MMP-9 (92 kDa, upper band) and the latent form of MMP-2 (72 kDa, lower band). The serum MMP-9 activities of SSc patients were higher than those of healthy controls. Densitometric analysis in sera of 20 SSc patients and 10 healthy controls indicated that the mean MMP-9 activity for SSc patients was 137.2 ± 21.7 densitometry units and for healthy controls, 38.5 ± 4.2 densitometry units (P < 0.001). Furthermore, a good linear correlation was found between the densitometry units measured by zymogram and the respective concentrations of MMP-9 measured by immunoassay in the sera of SSc patients (r = 0.875 and P < 0.001; data not shown). However, the intensity of the 86 kDa band (active MMP-9) was generally weak and was often not measurable.


Elevated matrix metalloproteinase-9 in patients with systemic sclerosis.

Kim WU, Min SY, Cho ML, Hong KH, Shin YJ, Park SH, Cho CS - Arthritis Res. Ther. (2004)

Gelatinase activity of matrix metalloproteinase (MMP)-2 (72 kDa) and MMP-9 (92 kDa) in sera of patients with systemic sclerosis (SSc) and healthy controls. Sera (0.5 μl) from 20 patients with SSc and 10 healthy controls were analyzed for their MMP-2 and MMP-9 activities by gel zymography. As a positive control, supernatants from cultured HT1080 cell lines (HT) stimulated with 10 μg/ml of concanavalin A were used. Numbers in parentheses are MMP-9 concentrations (ng/ml) determined by ELISA. The figure shows representative results for serum samples from the two groups.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1064883&req=5

Figure 3: Gelatinase activity of matrix metalloproteinase (MMP)-2 (72 kDa) and MMP-9 (92 kDa) in sera of patients with systemic sclerosis (SSc) and healthy controls. Sera (0.5 μl) from 20 patients with SSc and 10 healthy controls were analyzed for their MMP-2 and MMP-9 activities by gel zymography. As a positive control, supernatants from cultured HT1080 cell lines (HT) stimulated with 10 μg/ml of concanavalin A were used. Numbers in parentheses are MMP-9 concentrations (ng/ml) determined by ELISA. The figure shows representative results for serum samples from the two groups.
Mentions: We used gel zymography to study sera of 20 SSc patients and 10 healthy controls, all selected unsystematically, to ascertain the serum gelatinase activity of MMP-9. As can be seen in Fig. 3, the 92 kDa band, consistent with the latent form of MMP-9, was detected in the sera of all subjects. The bands in Fig. 3 represent the latent form of MMP-9 (92 kDa, upper band) and the latent form of MMP-2 (72 kDa, lower band). The serum MMP-9 activities of SSc patients were higher than those of healthy controls. Densitometric analysis in sera of 20 SSc patients and 10 healthy controls indicated that the mean MMP-9 activity for SSc patients was 137.2 ± 21.7 densitometry units and for healthy controls, 38.5 ± 4.2 densitometry units (P < 0.001). Furthermore, a good linear correlation was found between the densitometry units measured by zymogram and the respective concentrations of MMP-9 measured by immunoassay in the sera of SSc patients (r = 0.875 and P < 0.001; data not shown). However, the intensity of the 86 kDa band (active MMP-9) was generally weak and was often not measurable.

Bottom Line: Serum MMP-9 concentrations were significantly higher in the diffuse type (n = 23) than the limited type of SSc (n = 19).The increased MMP-9 concentrations may be attributable to overproduction by dermal fibroblasts in SSc.These findings suggest that the enhanced production of MMP-9 may contribute to fibrogenic remodeling during the progression of skin sclerosis in SSc.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division 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

ABSTRACT
Matrix metalloproteinase-9 (MMP-9) has been implicated in the pathogenesis of cancer, autoimmune disease, and various pathologic conditions characterized by excessive fibrosis. In this study, we investigated the expression of MMP-9 and its clinical significance in systemic sclerosis (SSc). The patients (n = 42) with SSc had higher concentrations of MMP-9 and of tissue inhibitor of metalloproteinase-1 (TIMP-1) and a higher ratio of MMP-9 to TIMP-1 in sera than healthy controls (n = 32). Serum MMP-9 concentrations were significantly higher in the diffuse type (n = 23) than the limited type of SSc (n = 19). Serum concentrations of MMP-9 correlated well with the degree of skin involvement, as determined by the Rodnan score and with serum concentrations of transforming growth factor beta. Moreover, dermal fibroblasts from patients with SSc produced more MMP-9 than those from healthy controls when they were stimulated with IL-1beta, tumor necrosis factor alpha, or transforming growth factor beta. Such an increase in MMP-9 production was partially blocked by treatment with cyclosporin A. In summary, the serum MMP-9 concentrations were elevated in SSc patients and correlated well with skin scores. The increased MMP-9 concentrations may be attributable to overproduction by dermal fibroblasts in SSc. These findings suggest that the enhanced production of MMP-9 may contribute to fibrogenic remodeling during the progression of skin sclerosis in SSc.

Show MeSH
Related in: MedlinePlus