Bmp2 regulates Serpinb6b expression via cAMP/PKA/Wnt4 pathway during uterine decidualization

• Published in: Journal of cellular and molecular medicine 2020-06, Vol.24 (12), p.7023-7033
• Main Authors: Yu, Hai‐Fan, Zheng, Lian‐Wen, Yang, Zhan‐Qing, Wang, Yu‐Si, Huang, Ji‐Cheng, Liu, Shu, Yue, Zhan‐Peng, Guo, Bin
• Format: Article
• Language: English
• Subjects: Animals; Bmp2; Bone morphogenetic protein 2; Bone Morphogenetic Protein 2 - metabolism; cAMP‐PKA‐Wnt4 pathway; Cell activation; Cell Differentiation; Cell growth; Cell Proliferation; Cyclic AMP; Cyclic AMP - metabolism; Cyclic AMP-Dependent Protein Kinases - metabolism; Decidua; Decidua - metabolism; decidualization; Female; Gelatinase A; Gelatinase B; Gonads; Hybridization; Kinases; Matrix Metalloproteinases - metabolism; Mice; Original; Physiology; Plasmids; Pregnancy; Protein kinase A; RNA, Messenger - genetics; RNA, Messenger - metabolism; Serpinb6b; Serpins - genetics; Serpins - metabolism; Signal Transduction; siRNA; Somatic cells; Stromal cells; Stromal Cells - cytology; Stromal Cells - metabolism; uterine stromal cell; Uterus; Wnt protein; Wnt4 Protein - metabolism
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.15372

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.