Objective: To observe the changes of matrix metalloproteinase-1,2/tissue inhibitor of metalloproteinase-1,2 (MMP-1,2 and TIMP-1,2) in granulation tissue after 30% TBSA deeper partial thickness scald, and explore the regulation mechanism of MMP-2/TIMP-2 during wound healing.
Methods: 150 male Wistar rats were randomly divided into 5 groups as follows: (1) normal control (n = 6); (2) injured control group (n = 36): which is subdivided into postburn 3 h, 6 h, 1 d, 3 d, 7 d and 14 d groups, respectively; (3) BDM group (n = 36): intravenous injected of 400 mg 2,3-butanedione monoxime in each rat was done after anesthesia; (4) H7 group (n = 36): Each rat was intravenous injected of 0.2 mg 1-5-isoquinolinyl-sulfony-2-methylpiperazine after anesthesia; (5) anti-c-fos group (n = 36): Each rat was intravenous injected of 5 microg c-fos monoclony antibody after anesthesia. The immunohistochemistry staining technique and the reverse transcription polymerase chain reaction (RT-PCR) were used for detecting.
Results: The expression of c-fos mRNA and protein was increased from 3 to 6 hours post-burn, and then decreased. The expression of MMP-1,2/TIMP-1,2 was delayed to 3 days post-burn compared with the expression of c-fos mRNA and protein. Treatment with BDM induced to raise c-fos mRNA and protein expression. The expression of MMP-1,2/TIMP-1,2 was also increased accordingly. However, following treatment with H7 inhibited the expression of c-fos mRNA and protein, MMP-1,2/TIMP-1,2 proteins expression decreased. Exogenous c-fos antibody could inhibit endogenous c-fos protein expression and the expression of MMP-1/TIMP-1,2 decreased, but MMP-2 has no notable changes.
Conclusions: The expression of MMP-1,2 and TIMP-1,2 has closely relation protein kinases activated signaling pathways. The expression changes of MMP-1 and TIMP-1/TIMP-2 depend on c-fos expression. Oncogenes play an important role in the change process of wound matrix degradation and remodeling.