期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 39, 期 11, 页码 3251-3266出版社
WILEY
DOI: 10.1002/eji.200939264
关键词
Apoptosis; Gadd45 gamma; Glomerular mesangial cells; Sublytic C5b-9; Thy-1 nephritis
类别
资金
- National Natural Science Foundations of China [30571728, 30772016]
- Ministry of Education of China [20060312005]
The complement C5b-9 complexes can result in cell apoptosis, but the mechanism of sublytic C5b-9-mediated glomerular mesangial cell (GMC) apoptosis in Thy-1 nephritis (Thy-1N) remains largely unclear. The Gadd45 gene is involved in the cellular response to DNA damage and can promote cell apoptosis. In this study, both Gadd45 gamma expression patterns and pathologic changes of renal tissue were examined in rat Thy-1N. Both Gadd45 gamma expression and GMC apoptosis were significantly decreased in Thy-1N rats upon the depletion of complement with cobra venom factor. Our in vitro studies showed that Gadd45 gamma over-expression increased sublytic C5b-9-induced GMC apoptosis, while Gadd45 gamma gene knockdown by siRNA greatly reduced GMC apoptosis. Moreover, Gadd45 gamma gene silencing in vivo markedly inhibited the pathologic changes in the renal tissue of Thy-1N rats. These data suggest that Gadd45 gamma gene expression is involved in regulating GMC apoptosis mediated by sublytic C5b-9 in Thy-1N.
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