TBX2, a Novel Regulator of Labour.
| Autor: | Fernando F; Reproductive Biology Laboratory, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands., Veenboer GJM; Reproductive Biology Laboratory, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands., Oudijk MA; Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands., Kampman MAM; Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands., Heida KY; Department of Obstetrics, Division of Woman and Baby, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands., Lagendijk LJM; Reproductive Biology Laboratory, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands., van der Post JAM; Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands., Jongejan A; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands., Afink GB; Reproductive Biology Laboratory, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands., Ris-Stalpers C; Reproductive Biology Laboratory, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.; Department of Obstetrics and Gynaecology, Amsterdam Reproduction and Development, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. |
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| Jazyk: | angličtina |
| Zdroj: | Medicina (Kaunas, Lithuania) [Medicina (Kaunas)] 2021 May 21; Vol. 57 (6). Date of Electronic Publication: 2021 May 21. |
| DOI: | 10.3390/medicina57060515 |
| Abstrakt: | Background and Objectives : Therapeutic interventions targeting molecular factors involved in the transition from uterine quiescence to overt labour are not substantially reducing the rate of spontaneous preterm labour. The identification of novel rational therapeutic targets are essential to prevent the most common cause of neonatal mortality. Based on our previous work showing that Tbx2 (T-Box transcription factor 2) is a putative upstream regulator preceding progesterone withdrawal in mouse myometrium, we now investigate the role of TBX2 in human myometrium. Materials and Methods : RNA microarray analysis of (A) preterm human myometrium samples and (B) myometrial cells overexpressing TBX2 in vitro, combined with subsequent analysis of the two publicly available datasets of (C) Chan et al. and (D) Sharp et al. The effect of TBX2 overexpression on cytokines/chemokines secreted to the myometrium cell culture medium were determined by Luminex assay. Results : Analysis shows that overexpression of TBX2 in myometrial cells results in downregulation of TNFα- and interferon signalling. This downregulation is consistent with the decreased expression of cytokines and chemokines of which a subset has been previously associated with the inflammatory pathways relevant for human labour. In contrast, CXCL5 (C-X-C motif chemokine ligand 5), CCL21 and IL-6 (Interleukin 6), previously reported in relation to parturition, do not seem to be under TBX2 control. The combined bioinformatical analysis of the four mRNA datasets identifies a subset of upstream regulators common to both preterm and term labour under control of TBX2. Surprisingly, TBX2 mRNA levels are increased in preterm contractile myometrium. Conclusions : We identified a subset of upstream regulators common to both preterm and term labour that are activated in labour and repressed by TBX2. The increased TBX2 mRNA expression in myometrium collected during a preterm caesarean section while in spontaneous preterm labour compared to tissue harvested during iatrogenic preterm delivery does not fit the bioinformatical model. We can only explain this by speculating that the in vivo activity of TBX2 in human myometrium depends not only on the TBX2 expression levels but also on levels of the accessory proteins necessary for TBX2 activity. |
| Databáze: | MEDLINE |
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