Functional similarity between TGF-beta type 2 and type 1 receptors in the female reproductive tract.
Functional similarity between TGF-beta type 2 and type 1 receptors in the female reproductive tract.
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DOI：
10.1038/s41598-021-88673-y
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发表时间：
2021-04-29
影响因子：
4.6
通讯作者：
Li Q
中科院分区：
文献类型：
--
作者：
Ni N;Fang X;Li Q
转化生长因子β（Transforming growth factor β，TGFβ）信号转导在生殖发育和生殖功能中起着关键作用。TGFβ配体通过TGFβ 2型受体（TGFBR 2）/TGFBR 1复合物传递信号。由于TGFBR 2和TGFBR 1在配体刺激后形成信号传导复合物，因此预期它们对于传播引发细胞应答的TGFβ信号传导同样重要。然而，一些遗传学研究挑战了这一概念，并表明TGFBR 2或TGFBR 1的破坏可能导致相反的表型结果。我们已经表明，使用抗苗勒管激素受体2型（Amhr 2）-Cre的Tgfbr 1的条件性缺失导致输卵管和子宫肌层缺陷。为了确定雌性生殖道中TGFBR 2的功能需求以及由任一受体的条件性消融引起的潜在表型差异/相似性，我们使用先前用于靶向Tgfbr 1的相同Cre驱动程序产生了携带Tgfbr 2缺失的小鼠。在此，我们发现，Tgfbr 2的条件性缺失导致类似的表型Tgfbr 1缺失在女性生殖道。此外，在Tgfbr 2缺失的子宫中遗传去除Tgfbr 1对Tgfbr 2条件性敲除小鼠的表型影响极小。总之，我们的研究结果揭示了TGFBR 2和TGFBR 1在维持女性生殖道结构完整性方面的功能相似性。
Transforming growth factor β (TGFβ) signaling plays critical roles in reproductive development and function. TGFβ ligands signal through the TGFβ receptor type 2 (TGFBR2)/TGFBR1 complex. As TGFBR2 and TGFBR1 form a signaling complex upon ligand stimulation, they are expected to be equally important for propagating TGFβ signaling that elicits cellular responses. However, several genetic studies challenge this concept and indicate that disruption of TGFBR2 or TGFBR1 may lead to contrasting phenotypic outcomes. We have shown that conditional deletion of Tgfbr1 using anti-Mullerian hormone receptor type 2 (Amhr2)-Cre causes oviductal and myometrial defects. To determine the functional requirement of TGFBR2 in the female reproductive tract and the potential phenotypic divergence/similarity resulting from conditional ablation of either receptor, we generated mice harboring Tgfbr2 deletion using the same Cre driver that was previously employed to target Tgfbr1. Herein, we found that conditional deletion of Tgfbr2 led to a similar phenotype to that of Tgfbr1 deletion in the female reproductive tract. Furthermore, genetic removal of Tgfbr1 in the Tgfbr2-deleted uterus had minimal impact on the phenotype of Tgfbr2 conditional knockout mice. In summary, our results reveal the functional similarity between TGFBR2 and TGFBR1 in maintaining the structural integrity of the female reproductive tract.
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