Increased serum levels and tissue expression of matrix metalloproteinase-12 in patients with systemic sclerosis: correlation with severity of skin and pulmonary fibrosis and vascular damage

Abstract

MMP-12 levels are increased in patients with SSc and are associated with severity of skin and pulmonary fibrosis and peripheral vascular damage.

Endothelial Cells Recruit Macrophages and Contribute to a Fibrotic Milieu in Bleomycin Lung Injury

“…In isolated endothelial cells from the lungs of BLM-injected mice, we observed a marked up-regulation in MMP12, which was significant at 4 weeks (Figure 2A). These data suggest that endothelial cells are damaged in this model of chronic lung injury, similar to the endothelial damage associated with SSc (22,23).…”

“…We observed an increase of vWF expression in endothelial cells, suggesting injury to the endothelium. In a recent report by Manetti and colleagues (23), increased MMP12 in the serum of patients with scleroderma correlated with the severity of pulmonary fibrosis and vascular injury. Consistent with this, we found that MMP12 was up-regulated in endothelial cells from mice treated with BLM.…”

“…MMP12 is increased in the skin and serum during SSc, and correlates with vascular damage and pulmonary fibrosis (23). MMP12 is most highly expressed in macrophages, but was shown to be induced in many different cell types, including endothelial cells, during SSc-ILD (23). In isolated endothelial cells from the lungs of BLM-injected mice, we observed a marked up-regulation in MMP12, which was significant at 4 weeks (Figure 2A).…”

“…As a second marker of endothelial injury, we analyzed matrix metallopeptidase (MMP)-12. MMP12 is increased in the skin and serum during SSc, and correlates with vascular damage and pulmonary fibrosis (23). MMP12 is most highly expressed in macrophages, but was shown to be induced in many different cell types, including endothelial cells, during SSc-ILD (23).…”

Increased plasma soluble urokinase plasminogen activator receptor levels in systemic sclerosis: possible association with microvascular abnormalities and extent of fibrosis

“…Biomarkers of endothelial dysfunction and impaired angiogenesis have been also suggested in SSc. These include ADAMTS-13 enzyme, endothelin-1, endothelial growth factor receptor-1 and -7, and matrix metalloproteinase-12 [3,4].…”