TGF beta 1 attenuates expression of prolactin and IGFBP-1 in decidualized endometrial stromal cells by both SMAD-dependent and SMAD-independent pathways

Kane, N.M., Jones, M., Brosens, J.J., Kelly, R.W., Saunders, P.T.K. and Critchley, H.O.D. (2010) TGF beta 1 attenuates expression of prolactin and IGFBP-1 in decidualized endometrial stromal cells by both SMAD-dependent and SMAD-independent pathways. PLoS ONE, 5(9), e12970. (doi: 10.1371/journal.pone.0012970) (PMID:20885978) (PMCID:PMC2945765)

Abstract

Background: Decidualization (differentiation) of the endometrial stromal cells during the secretory phase of the menstrual cycle is essential for successful implantation. Transforming Growth Factor beta 1 (TGF beta 1) canonically propagates its actions via SMAD signalling. A role for TGF beta 1 in decidualization remains to be established and published data concerning effects of TGF beta 1 on markers of endometrial decidualization are inconsistent. Methodology/Principal Findings: Non-pregnant endometrial stromal cells (ESC) and first trimester decidual stromal cells (DSC) were cultured in the presence or absence of a decidualizing stimulus. Incubation of ESCs with TGF beta 1 (10 ng/ml) down-regulated the expression of transcripts encoding the decidual marker proteins prolactin (PRL), insulin-like growth factor binding protein-1 (IGFBP-1) and tissue factor (TF). TGF beta 1 also inhibited secretion of PRL and IGFBP-1 proteins by ESCs and surprisingly this response preceded down-regulation of their mRNAs. In contrast, DSCs were more refractory to the actions of TGF beta 1, characterized by blunted and delayed down-regulation of PRL, IGFBP-1, and TF transcripts, which was not associated with a significant reduction in secretion of PRL or IGFBP-1 proteins. Addition of an antibody directed against TGF beta 1 increased expression of IGFBP-1 mRNA in decidualised cells. Knockdown of SMAD 4 using siRNAs abrogated the effect of TGF beta 1 on expression of PRL in ESCs but did not fully restore expression of IGFBP-1 mRNA and protein. Conclusions/Significance: TGF beta 1 inhibits the expression and secretion of decidual marker proteins. The impact of TGF beta 1 on PRL is SMAD-dependent but the impact on IGFBP1 is via an alternative mechanism. In early pregnancy, resistance of DSC to the impact of TGF beta 1 may be important to ensure tissue homeostasis.

• Item Type: Articles
• Additional Information: This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Kane, Dr Nicole
• Authors: Kane, N.M., Jones, M., Brosens, J.J., Kelly, R.W., Saunders, P.T.K., and Critchley, H.O.D.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Published Online: 01 January 2010
• Copyright Holders: © 2010 Kane et al
• First Published: First published in PLoS ONE 2010 5(9): e12970
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher