Apoptosis of glomerular mesangial cells induced by sublytic C5b‐9 complexes in rats with Thy‐1 nephritis is dependent on Gadd45γ 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 Gadd45γ expression patterns and pathologic changes of renal tissue were examined in rat Thy‐1N. Both Gadd45γ 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 Gadd45γ over‐expression increased sublytic C5b‐9‐induced GMC apoptosis, while Gadd45γ gene knockdown by siRNA greatly reduced GMC apoptosis. Moreover, Gadd45γ gene silencing in vivo markedly inhibited the pathologic changes in the renal tissue of Thy‐1N rats. These data suggest that Gadd45γ gene expression is involved in regulating GMC apoptosis mediated by sublytic C5b‐9 in Thy‐1N.