Bmp2 regulates Serpinb6b expression via cAMP/PKA/Wnt4 pathway during uterine decidualization
Bmp2 regulates Serpinb6b expression via cAMP/PKA/Wnt4 pathway during uterine decidualization
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DOI：
10.1111/jcmm.15372
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发表时间：
2020-05
影响因子：
5.3
通讯作者：
Hai-Fan Yu;Lian-wen Zheng;Zhan‐Qing Yang;Yu‐Si Wang;Ji-Cheng Huang;Shu Liu;Z. Yue;B. Guo
中科院分区：
文献类型：
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作者：
Hai-Fan Yu;Lian-wen Zheng;Zhan‐Qing Yang;Yu‐Si Wang;Ji-Cheng Huang;Shu Liu;Z. Yue;B. Guo
Serpinb6b是Serpinb家族的新成员，在小鼠性腺的生殖细胞和体细胞中发现，但其在子宫蜕膜化中的生理功能仍不清楚。本研究表明，蜕膜细胞中含有丰富的 Serpinb6b，并促进基质细胞的增殖和分化，表明 Serpinb6b 在子宫蜕膜化中发挥着创造性作用。进一步分析发现Serpinb6b调节Mmp2和Mmp9的表达。同时，Serpinb6b 被确定为基质分化中 Bmp2 调节的靶标。 rBmp2 处理导致细胞内 cAMP 水平积累，其在此分化程序中的功能由 Serpinb6b 介导。添加 PKA 抑制剂 H89 阻碍了 Bmp2 对 Serpinb6b 的诱导，而 8-Br-cAMP 则挽救了 Bmp2 敲低引起的 Serpinb6b 表达缺陷。 Serpinb6b 的减弱极大地减少了基质细胞分化中组成型 Wnt4 激活的诱导。相比之下，Serpinb6b 的过表达阻止了 Wnt4 siRNA 对分化过程的抑制。此外，阻断 Wnt4 消除了 Serpinb6b 上 cAMP 的上调。总的来说，Serpinb6b 通过 Mmp2/9 响应 Bmp2/cAMP/PKA/Wnt4 途径介导子宫蜕膜化。
Serpinb6b is a novel member of Serpinb family and found in germ and somatic cells of mouse gonads, but its physiological function in uterine decidualization remains unclear. The present study revealed that abundant Serpinb6b was noted in decidual cells, and advanced the proliferation and differentiation of stromal cells, indicating a creative role of Serpinb6b in uterine decidualization. Further analysis found that Serpinb6b modulated the expression of Mmp2 and Mmp9. Meanwhile, Serpinb6b was identified as a target of Bmp2 regulation in stromal differentiation. Treatment with rBmp2 resulted in an accumulation of intracellular cAMP level whose function in this differentiation program was mediated by Serpinb6b. Addition of PKA inhibitor H89 impeded the Bmp2 induction of Serpinb6b, whereas 8‐Br‐cAMP rescued the defect of Serpinb6b expression elicited by Bmp2 knock‐down. Attenuation of Serpinb6b greatly reduced the induction of constitutive Wnt4 activation on stromal cell differentiation. By contrast, overexpression of Serpinb6b prevented this inhibition of differentiation process by Wnt4 siRNA. Moreover, blockage of Wnt4 abrogated the up‐regulation of cAMP on Serpinb6b. Collectively, Serpinb6b mediates uterine decidualization via Mmp2/9 in response to Bmp2/cAMP/PKA/Wnt4 pathway.