Bridgham J T, Johnson A L
Department of Biological Sciences and the Walther Cancer Research Center, The University of Notre Dame, Notre Dame, Indiana 46556, USA.
Biol Reprod. 2004 Apr;70(4):972-9. doi: 10.1095/biolreprod.103.023614. Epub 2003 Nov 26.
As a result of searching recently available chicken (ch) expressed sequence tag databases, a new Tumor Necrosis Factor Receptor Super Family (TNFRSF) member with similarity to the murine (m) TNFRSF23 decoy receptor (DcR) has been identified. However, by comparison with the mTNFRSF23, there exist at least two splice variants of chTNFRSF23, one of which includes an intracellular death domain (TNFRSF23.v1) characteristic of death receptors, and the other with a truncated cytoplasmic domain of a DcR (named TNFRSF23.v2). These two splice variants of chTNFRSF23 display differential patterns of mRNA expression across various hen tissues, with the highest levels observed within reproductive tissues. More specifically, TNFRSF23.v1 is most highly expressed in preovulatory follicle granulosa cells in the ovary, whereas TNFRSF23.v2 mRNA is found at highest levels in ovarian stromal tissue. Primary culture experiments with granulosa cells determined that expression of TNFRSF23.v1 mRNA was decreased by protein kinase A signaling and enhanced by transforming growth factor (TGF) alpha treatment. Interestingly, TGFbeta1 and signaling via protein kinase C also enhanced levels of TNFRSF23.v1 expression but only in undifferentiated granulosa cells from prehierarchal follicles. Based on patterns of mRNA expression and its endocrine/paracrine regulation, we predict that ovarian chTNFRSF23 represents a modulator of granulosa cell survival and/or differentiation. Finally, the characterization of these receptor variants is of considerable interest from an evolutionary perspective in that they provide additional evidence to support a continuing divergence of TNFRSF members throughout vertebrate evolution.
通过检索近期可用的鸡(ch)表达序列标签数据库,已鉴定出一种与小鼠(m)肿瘤坏死因子受体超家族(TNFRSF)23型诱饵受体(DcR)相似的新型TNFRSF成员。然而,与mTNFRSF23相比,chTNFRSF23至少存在两种剪接变体,其中一种包含死亡受体特有的细胞内死亡结构域(TNFRSF23.v1),另一种具有DcR的截短细胞质结构域(命名为TNFRSF23.v2)。chTNFRSF23的这两种剪接变体在鸡的各种组织中呈现出不同的mRNA表达模式,在生殖组织中观察到的表达水平最高。更具体地说,TNFRSF23.v1在卵巢排卵前卵泡颗粒细胞中表达最高,而TNFRSF23.v2 mRNA在卵巢基质组织中水平最高。对颗粒细胞进行的原代培养实验表明,蛋白激酶A信号传导可降低TNFRSF23.v1 mRNA的表达,而转化生长因子(TGF)α处理可增强其表达。有趣的是,TGFβ1和蛋白激酶C信号传导也可增强TNFRSF23.v1的表达水平,但仅在来自前等级卵泡的未分化颗粒细胞中如此。基于mRNA表达模式及其内分泌/旁分泌调节,我们预测卵巢chTNFRSF23代表颗粒细胞存活和/或分化的调节因子。最后,从进化角度来看,这些受体变体的特征具有相当大的研究价值,因为它们提供了额外的证据来支持TNFRSF成员在整个脊椎动物进化过程中持续分化。