Objective: To investigate the expression characteristics of matrix metalloproteinases (MMP-2, MMP-3, MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1, TIMP-2) in developing fetal skin and their potential biological significance.
Methods: Skin of 24 cases of fetuses with different gestational age (12-40 weeks) were obtained, embedded with paraffin wax, and sectioned. Immunohistochemistry and pathological methods were used to detect the expression intensity and distribution of MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2.
Results: Positive immunohistochemical signals of MMPs and TIMPs could be found in fetal skin at different gestational periods. These proteins mainly located in the cytoplasm of epidermal cells, fibroblasts, epithelial cells of hair follicles and sweat glands and vascular endothelial cells. In earlier gestational fetal skin (12-18 weeks), the expression levels of MMP-2, MMP-3 and MMP-9 were high. Along with the advancement in gestational age, the positive rates of these three proteins in skin were lowered, and in later gestational fetal skin (27-40 weeks) the expression rates were significantly decreased compared with those in earlier gestational fetal skin (all P<0.05). On the contrary, protein expression levels of TIMP-1 and TIMP-2 were apparently lower in earlier versus later gestational skin (both P<0.05).
Conclusion: MMP-2, MMP-3, MMP-9, TIMP-1 and TIMP-2 might be involved in the skin development and maintenance of cutaneous structure and function. Higher expression of MMP-2, MMP-3 and MMP-9 and lower protein levels of TIMP-1 and TIMP-2 may provide an antiscarring signal in healing of wound during early periods of gestation.