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Published on: April 22, 2014
Expression of matrix metalloproteinase and its tissue inhibitor in haemangioma
Shan Zhong1, Guohua Yang, Cong Xia
1Basic Medical School, Wuhan University, Wuhan, 430071, China. zhongshan@whu.edu.cn
Abstract:
The action mechanism of matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in the genesis, development and degeneration of haemangioma was investigated by detecting their expression in the tissue of haemangioma in different phases by using the immunohistochemistry. Fifty paraffin-embedded specimens of skin capillary haemangioma were collected, which were documented in the Department of Pathology, Renmin Hospital of Wuhan University from 2000 to 2006. All samples were stained by regular HE method, and proliferative cell nuclear antigen (PCNA) was tested by immunohistochemical S-P method. The samples were classified according to the Mulliken criteria and the expression pattern of PCNA. Immunohistochemical S-P method was applied to detect the expression of MMP-2 and TIMP-2 in proliferative and degenerative phases of cutaneous capillary haemangioma, and in normal skin tissues. In combination with the detection of the expression of factor VIII-related antigen, it was verified that in haemangioma tissues, the cells expressing MMP-2 and TIMP-2 were vascular endothelial cells. The MMP-2 and TIMP-2 expression was quantitatively analyzed by image analysis system (HPIAS-1000), and one-way ANOVA(107) and SNK(q) test were done to analyze average absorbance (A) and positive area rate of immunohistochemically positive particles by using SPSS11.5. The results showed: (1) Among 50 samples of haemangioma, there were 26 proliferative haemangiomas, and 24 degenerative haemangiomas, respectively; (2) The expression of MMP-2 was weak in normal vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression of MMP-2 in proliferative group was significantly higher than in degenerative group and control group (normal skin) (P<0.05), but there was no statistically significant difference between the latter two groups; (3) TIMP-2 was highly expressed in normal tissues, degenerative vascular endothelial cells, cytoplasm of connective tissues and extracellular matrix around blood vessels. The expression level of TIMP-2 in proliferative phase was significantly lower than in degenerative phase (P<0.05), and the expression of TIMP-2 in proliferative phase was significantly different from that in degenerative phase and normal tissues (P<0.05). It was concluded that in proliferative phase of haemangioma, MMP-2 may promote over-proliferation of endothelial cells of haemangioma, and in degenerative phase, TIMP-2 can inhibit the proliferation of endothelial cells of haemangioma. The two substances play important roles in the genesis, development and degeneration of haemangiomas.
Insights
Matrix metalloproteinases-2 (MMP-2) promotes haemangioma cell proliferation, while tissue inhibitor of metalloproteinases-2 (TIMP-2) inhibits it. These proteins are key to haemangioma development and degeneration.
Area of Science:
- Vascular biology
- Oncology
- Biochemistry
Background:
- Haemangiomas are benign vascular tumors with distinct proliferative and degenerative phases.
- The roles of matrix metalloproteinases-2 (MMP-2) and tissue inhibitor of metalloproteinases-2 (TIMP-2) in haemangioma pathogenesis are not fully elucidated.
Purpose of the Study:
- To investigate the expression and action mechanisms of MMP-2 and TIMP-2 in different phases of cutaneous capillary haemangioma.
- To determine the cellular origin of MMP-2 and TIMP-2 expression in haemangioma tissues.
Main Methods:
- Immunohistochemistry was used to detect MMP-2 and TIMP-2 expression in 50 haemangioma specimens and normal skin.
- Samples were classified into proliferative and degenerative phases using Mulliken criteria and PCNA expression.
- Factor VIII-related antigen confirmed vascular endothelial cell expression of MMP-2 and TIMP-2.
- Quantitative analysis of protein expression was performed using an image analysis system.
Main Results:
- MMP-2 expression was significantly higher in the proliferative phase compared to the degenerative and normal skin groups.
- TIMP-2 expression was significantly lower in the proliferative phase than in the degenerative and normal skin groups.
- MMP-2 and TIMP-2 were localized to vascular endothelial cells in haemangioma tissues.
Conclusions:
- MMP-2 promotes endothelial cell over-proliferation during the proliferative phase of haemangioma.
- TIMP-2 inhibits endothelial cell proliferation during the degenerative phase of haemangioma.
- MMP-2 and TIMP-2 play critical roles in the genesis, development, and degeneration of haemangiomas.
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