Bone morphogenetic proteins(BMPs) play a critical role in the growth and steroidogenesis of granulosa cells(GCs).BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors.Upon ligand binding...Bone morphogenetic proteins(BMPs) play a critical role in the growth and steroidogenesis of granulosa cells(GCs).BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors.Upon ligand binding,BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types.The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs.A strategy of RNA interference(RNAi)-mediated 'gene silencing' of Smad4,a core molecule mediating the intracellular BMP/Smad signal transduction pathways,was used to interrupt endogenous BMP/Smad signaling.Results indicate that Smad4-small interfering RNA(siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection.Interrupted endogenous BMP/Smad signaling significantly inhibited growth,and induced apoptosis of porcine GCs,while decreasing estradiol production.In addition,interrupted BMP/Smad signaling significantly(P<0.05) changed the expression of Cyclin D2,CDK4,Bcl-2,and Cyp19a1.These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.展开更多
基金(No. 2006AA10Z136) supported by National High-Tech R & D Program (863) of China
文摘Bone morphogenetic proteins(BMPs) play a critical role in the growth and steroidogenesis of granulosa cells(GCs).BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors.Upon ligand binding,BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types.The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs.A strategy of RNA interference(RNAi)-mediated 'gene silencing' of Smad4,a core molecule mediating the intracellular BMP/Smad signal transduction pathways,was used to interrupt endogenous BMP/Smad signaling.Results indicate that Smad4-small interfering RNA(siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection.Interrupted endogenous BMP/Smad signaling significantly inhibited growth,and induced apoptosis of porcine GCs,while decreasing estradiol production.In addition,interrupted BMP/Smad signaling significantly(P<0.05) changed the expression of Cyclin D2,CDK4,Bcl-2,and Cyp19a1.These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.