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Publication : Ptn functions downstream of C/EBPβ to mediate the effects of cAMP on uterine stromal cell differentiation through targeting Hand2 in response to progesterone.

First Author  Yu HF Year  2018
Journal  J Cell Physiol Volume  233
Issue  2 Pages  1612-1626
PubMed ID  28657144 Mgi Jnum  J:273547
Mgi Id  MGI:6294220 Doi  10.1002/jcp.26067
Citation  Yu HF, et al. (2018) Ptn functions downstream of C/EBPbeta to mediate the effects of cAMP on uterine stromal cell differentiation through targeting Hand2 in response to progesterone. J Cell Physiol 233(2):1612-1626
abstractText  Ptn is a pleiotropic growth factor involving in the regulation of cellular proliferation and differentiation, but its biological function in uterine decidualization remains unknown. Here, we showed that Ptn was highly expressed in the decidual cells, and could induce the proliferation of uterine stromal cells and expression of Prl8a2 and Prl3c1 which were two well-established differentiation markers for decidualization, suggesting an important role of Ptn in decidualization. In the uterine stromal cells, progesterone stimulated the expression of Ptn accompanied with an accumulation of intracellular cAMP level. Silencing of Ptn impeded the induction of progesterone and cAMP on the differentiation of uterine stromal cells. Administration of PKA inhibitor H89 resulted in a blockage of progesterone on Ptn expression. Further analysis evidenced that regulation of progesterone and cAMP on Ptn was mediated by C/EBPbeta. During in vitro decidualization, knockdown of Ptn could weaken the up-regulation of Prl8a2 and Prl3c1 elicited by C/EBPbeta overexpression, while constitutive activation of Ptn reversed the repressive effects of C/EBPbeta siRNA on the expression of Prl8a2 and Prl3c1. Meanwhile, Ptn might mediate the regulation of C/EBPbeta on Hand2 which was a downstream target of Ptn in the differentiation of uterine stromal cells. Attenuation of Ptn or C/EBPbeta by specific siRNA blocked the stimulation of Hand2 by progesterone and cAMP. Collectively, Ptn may play a vital role in the progesterone-induced decidualization pathway.
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