Characteristics and implication of MMP-12 expression during the course of development of radiation pulmonary injuries / 解放军医学杂志

ABSTRACT

Objective To observe the dynamic changes in matrix metalloproteinase-12(MMP-12) expression during the course of development of radiation pulmonary injuries in order to get an insight of the roles played by MMP-12 during early tissue remodeling after radiation pulmonary injuries.Methods Twenty-four Wistar rats were randomly assigned into four groups(6 each) normal control group and 1,2 and 4 weeks after irradiation groups.The rats in the last three groups received irradiation of the whole lung with 20Gy of 60Co ?-ray,and they were sacrificed 1,2 and 4 weeks post irradiation.The gene expression of MMP-12 was determined by RT-PCR;the protein expression was detected by Western blot;MMP-12 activity was examined by gelatin zymography;the tissue distribution of MMP-12 was observed by immunohistochemistry;the degradation and collapse of elastin were observed after tissue elastin specific staining.Results The gene expression of MMP-12 began to increase 1 week post irradiation,then decreased at 2 weeks,and it reached its peak value at 4 weeks,while its protein expression was elevated again 2 weeks post irradiation.MMP-12 was mainly expressed in macrophages and activated fibroblasts of the alveolar septum.With the elapse of time,the lung injury aggravated gradually,with thickening of alveolar wall and septum,breakdown of the structure of alveoli,collapss of a part of the alveolar space,extensive breakdown of elastin in the basement membrane of lung,appearing as irregular fibrils distributed in the lung.Conclusion 60Co ?-ray irradiation can up-regulate the expression of gene and protein of MMP-12 significantly,implying that it may play a very important role in early remodeling process in of radiation pulmonary injuries,and initiate the process of pulmonary remodeling by degrading elastin and destroying the normal structure of basement membrane.