Effects of matrix metalloproteinase-12 abnormal expression on the transformation of pulmonary fibroblasts in radiation damaged rats

Objective To observe the effects of over-expression of matrix metalloproteinase-12 (MMP-12) on the transformation of pulmonary fibroblasts in radiation damaged rats. Methods Thirty-two male Wistar rats (weighed 250-280g) were randomly assigned into control group and 1, 2 and 4 weeks after irradiation groups (8 each). The whole lungs of rats in irradiation groups were irradiated by 60 Co γ-ray at a dose of 20Gy, and the lung specimens were harvested 1, 2 and 4 weeks after radiation. The change of MMP-12 activity was detected by gelatin zymography, the degradation and collapse of elastic fibers were observed by tissue specific staining, the cross talking phenomenon between alveolar type Ⅱ cells and mesenchymal cells was observed by transmission electron microscopy, the content of TGF-β1 was determined by ELISA, and the expression of α-smooth muscle actin (α-SMA) was examined by immunohistochemistry. Results MMP-12 activity began increasing 1 week after irradiation, and seemed to decrease 4 weeks after irradiation. Elastin, a part of the basement membrane of alveolar wall, began to degrade and collapse 1 week after radiation, and became worse 4 weeks after irradiation. The expressions of both TGF-β1 and α-SMA were elevated gradually within 4 weeks after radiation. The cross talking phenomenon was found by electron microscopy between alveolar type Ⅱ cells and mesenchymal cells. Conclusions Increased activity of pulmonary MMP-12 has been found after radiation, which may promote the transformation of pulmonary fibroblasts by degrading elastin and ultimately initiate the pulmonary fibrosis.