Apoptosis of glomerular mesangial cells induced by sublytic C5b-9 complexes in rats with Thy-1 nephritis is dependent on Gadd45 gamma upregulation.
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.
Qiu
Wen
W
Department of Microbiology and Immunology, Nanjing Medical University, Nanjing, Jiangsu, PR China.
Che
Nan
N
Feng
Xuefeng
X
Xia
Mei
M
Wang
Hui
H
Zhao
Dan
D
Wang
Yingwei
Y
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015153:Blotting, Western; D002469:Cell Separation; D015938:Complement Membrane Attack Complex / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020287:In Situ Nick-End Labeling; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology*; D050527:Mesangial Cells / Q000473:pathology*; D009393:Nephritis / Q000276:immunology* / Q000473:pathology; D034741:RNA, Small Interfering; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018800:Thy-1 Antigens / Q000276:immunology; D014162:Transfection; D015854:Up-Regulation; D000097642:GADD45 Proteins
D015938:Complement Membrane Attack Complex; D047908:Intracellular Signaling Peptides and Proteins; D034741:RNA, Small Interfering; D018800:Thy-1 Antigens; D000097642:GADD45 Proteins