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J Korean Soc Ther Radiol Oncol > Volume 21(1); 2003 > Article
The Journal of the Korean Society for Therapeutic Radiology and Oncology 2003;21(1): 66-74.
Expression of Matrix Metalloproteinase-2 and Tissue Inhibitor of Metalloproteinase-2 in Radiation Exposed Small Intestinal Mucosa of the Rat
Hyon Joo Kwag, Kyoung Ja Lee, Chung Sik Rhee
1Department of Diagnostic Radiology, Kangbuk Samsung Hospital, Sungkyunkwan University, radiokwag@hanmail.net
2Department of Radiation Oncology, Medical College, Ewha Womans University, Seoul, Korea.
3Department of Diagnostic Radiology, Medical College, Ewha Womans University, Seoul, Korea.
ABSTRACT
PURPOSE:
The matrix metalloproteinases (MMPs) are a family of enzymes whose main function is the degradation of the extracellular matrix. Several studies have revealed that MMPs and TIMPs are related to the wound healing process and in photoaging caused by ultraviolet irradiation. However, the expressions of MMP and TIMP after irradiation have not, to the best of our knowledge, been studied. This study investigates the expressions of MMP-2 and TIMP-2 in rat intestinal mucosa following irradiation. Material and
Methods:
The entire abdomen of Sprague-Dawley rats was irradiated using a single dose method. The rats were sacrificed on day 1, 2, 3, 5, 7 and 14 following irradiation. Histopathological observations were made using hematoxilin & eosin staining. The expressions of MMP-2 and TIMP-2 were examined using immunohistochemistry, immunoblotting and ELISA.
RESULTS:
Radiation induced damage, associated with atrophic villi, and infiltration of inflammatory cells was observed from the first postirradiation day, and severe tissue damage was observed on the second and the third postirradiation days. An increase in mitosis and the number of regenerating crypts, as evidence of regeneration, were most noticeable on the fifth postirradiation day. From the immunohistochemistry, the MMP-2 expression was observed from the first postirradiation day, but was most conspicuous on the third and the fifth postirradiation days. The TIMP-2 expression was most conspicuous on the fifth postirradiation day. From the immunoblotting, the MMP-2 expression was strongly positive on the third postirradiation day, and that of TIMP-2 showed a strong positive response on the fifth postirradiation day. In ELISA tests, the expressions of MMP-2 and TIMP-2 were increased in the postirradiation groups compared to those of the normal controls, and showed a maximum increase on the fifth postirradiation day. These results were statistically significant.
CONCLUSION:
The expressions of MMP-2 and TIMP-2 were increased in the intestinal mucosa of the rats following irradiation, and these results correlated with the histopathological findings, such as tissue damage and regeneration. Therefore, this study suggests that MMP-2 and TIMP-2 play roles in the mechanisms of radiation-induced damage and regeneration of intestinal mucosa of rats.
Key Words: Matrix metalloproteinase, Tissue inhibitor of metalloproteinase, Radiation, Rat small intestine
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