首页> 外文期刊>Reproduction: The official journal of the Society for the Study of Fertility >Transforming growth factor beta (TGFB) signaling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus–maternal interface
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Transforming growth factor beta (TGFB) signaling is activated during porcine implantation: proposed role for latency-associated peptide interactions with integrins at the conceptus–maternal interface

机译:猪植入过程中激活了转化生长因子β(TGFB)信号转导:在概念-母亲界面与潜伏期相关肽与整合素相互作用的拟议作用

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The process of implantation is mediated by a complex network of signaling and adhesive factors. In the pig, latent and active transforming growth factor beta (TGFB), TGFB receptors (TGFBR), and integrins (ITGs) are present during the peri-implantation period. TGFB signals via TGFBR and activates downstream effector SMAD proteins 2 and 3 (p-SMAD2/3). Latency-associated peptide (LAP), part of the latent TGFB complex, is known to bind to ITG heterodimers and activate TGFB. We hypothesize that active TGFBs and TGFBRs along with LAP and ITGs functionally interact at the conceptus–maternal interface to mediate events essential for conceptus development and attachment in pigs. Uteri and conceptuses from days 10, 12, 16, 20, and 24 pregnant gilts were immunostained for TGFB, LAP, and ITG subunits (ITGAV, ITGB1, ITGB3, ITGB5, ITGB6, and ITGB8). Activation of TGFBRs was evaluated by the presence of phosphorylated downstream effector SMAD2/3. Binding of LAP to ITGs was also evaluated using porcine trophectoderm cells. Abundant active TGFB was detected at the apical surfaces of epithelia at the conceptus–maternal interface, and p-SMAD2/3 was detected at both conceptus attachment and nonattachment sites during implantation. Separate aggregates of LAP, ITGB1, ITGB5, and later ITGB3 were detected at the porcine conceptus–maternal interface, and binding of LAP to ITGs on apical surfaces was demonstrated. Results suggest that functional LAP–ITG adhesion complexes support conceptus attachment and promote TGFB activation leading to TGFB interaction with TGFBR supporting events of porcine implantation.
机译:植入过程由信号和粘附因子的复杂网络介导。在猪的植入期间,存在潜在的和活跃的转化生长因子β(TGFB),TGFB受体(TGFBR)和整联蛋白(ITG)。 TGFB通过TGFBR发出信号并激活下游效应物SMAD蛋白2和3(p-SMAD2 / 3)。潜伏相关肽(LAP)是潜在TGFB复合物的一部分,已知与ITG异二聚体结合并激活TGFB。我们假设活跃的TGFB和TGFBR以及LAP和ITG在概念-母体界面上发生功能性相互作用,以介导对于猪概念发展和附着至关重要的事件。对TGFB,LAP和ITG亚基(ITGAV,ITGB1,ITGB3,ITGB5,ITGB6和ITGB8)的第10、12、16、20和24天妊娠小母猪的子宫和受孕进行了免疫染色。通过磷酸化的下游效应子SMAD2 / 3的存在来评估TGFBR的激活。还使用猪滋养外胚层细胞评估了LAP与ITG的结合。在概念-母体界面上皮的顶表面检测到大量的活性TGFB,在植入过程中在概念附着和非附着位置均检测到p-SMAD2 / 3。 LAP,ITGB1,ITGB5和后来的ITGB3的单独聚集体在猪概念-母亲界面处检测到,并证明了LAP与根尖表面上的ITG结合。结果表明功能性LAP–ITG粘附复合物支持概念附着并促进TGFB活化,从而导致TGFB与TGFBR相互作用,从而支持猪植入事件。

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