Molecular and cellular endocrinology
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Mol. Cell. Endocrinol. · Mar 2020
LncRNA HCP5 promotes cell proliferation and inhibits apoptosis via miR-27a-3p/IGF-1 axis in human granulosa-like tumor cell line KGN.
This study aimed to reveal the potential roles of long non-coding RNA HCP5 (lncRNA HCP5) and its potential molecular mechanism in polycystic ovarian syndrome (PCOS). The human granulosa-like tumor cell line KGN was used for assessing the effects of HCP5 in the proliferation and apoptosis of granulosa cells (GCs). The results showed that downregulation of HCP5 suppressed cell proliferation through arresting cell cycle progression at G1 phase, and induced the apoptosis via activating mitochondrial pathway, while overexpression of HCP5 played the opposite effects in KGN cells. ⋯ Additionally, miR-27a-3p inhibitor remarkably reversed the IGF-1 decrease regulated by knocking down HCP5 and miR-27a-3p mimics inhibited the IGF-1 increase modulated by overexpressing HCP5 in KGN cells. Furthermore, we observed that the promoted cell vitality and reduced apoptosis mediated by enforced expression of HCP5 could be alleviated when the KGN cells transfected with IGF-1 siRNA. Our findings indicate that HCP5 might be a potential regulatory factor for development of PCOS through regulating the miR-27a-3p/IGF-1 axis.
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Mol. Cell. Endocrinol. · Jan 2020
The impact of progesterone and RU-486 on classic pro-labour proteins & contractility in human myometrial tissues during 24-hour exposure to tension & interleukin-1β.
Increased expression of pro-labour genes that encode cyclooxygenase-2 (COX-2), oxytocin receptor (OTR) and connexin-43 (Cx43) at parturition is often attributed to P4 functional withdrawal, based on findings from animal models and human primary myometrial cells. However, the cause of reduced myometrial P4 responsiveness that promotes contractions at labour is not fully determined. Uterine stretch occurs with advancing gestation but most in vitro experimental models do not take this into consideration. ⋯ Interleukin-1β (IL-1β; 1 ng/ml) enhanced COX-2 protein and PGE2 content in un-stretched tissues. Overall, tissue stretch may, in part, regulate P4-sensitive pro-labour protein levels, but this is likely to be reliant on interaction with other in utero factors that were absent in our tissue cultures. More complex culture conditions should be evaluated in future to aid further development of a physiologically relevant model to improve our understanding of in utero myometrial P4 responsiveness.
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Mol. Cell. Endocrinol. · Apr 2019
Functional genomic analysis of the human receptive endometrium transcriptome upon administration of mifepristone at the time of follicle rupture.
The aim of this study was to analyze the effects of progesterone withdrawal on gene transcription in receptive endometrium by the administration of a single dose of 50 mg of the anti-progesterone receptor mifepristone (MFP) at the time of follicle rupture (FR). Six volunteer ovulatory women were studied, taking endometrial biopsies of three control and three MFP-treated women on days LH+2 (C-LH+2) and LH+7 (T-MFP), respectively. ⋯ The functional genomic analysis of the differentially expressed genes showed that MFP interfered negatively with the bio-functions decidualization of uterus and implantation of blastocyst and embryo. The results of this study confirm but also give new information on how MFP affects endometrial gene expression when administered at the time of FR and the dose used in emergency contraception.
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Mol. Cell. Endocrinol. · Jan 2019
Hydrogen sulfide primes diabetic wound to close through inhibition of NETosis.
Diabetes-induced neutrophil NETosis impairs wound healing through neutrophil extracellular traps (NETs). Reactive oxygen species (ROS)-triggered activation of mitogen-activated protein kinase (MAPK) ERK1/2 and p38 is involved in NETosis. Hydrogen sulfide (H2S), an endogenous signaling molecule, accelerates diabetic wound healing (DWH), and inhibits ROS production, ERK1/2 and p38 activation, while its level is decreased in diabetes. ⋯ The treatment with H2S not only attenuated ROS production but also abolished MAPK ERK1/2 and p38 activation. Like the effects of H2S, inhibition of MAPK ERK1/2 or p38 could decrease NETs release. These findings suggests that H2S attenuates NETosis and primes diabetic wound to heal through blockage of ROS-mediated MAPK ERK1/2 and p38 activation.
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Mol. Cell. Endocrinol. · Jan 2019
Progesterone and cAMP synergize to inhibit responsiveness of myometrial cells to pro-inflammatory/pro-labor stimuli.
Progesterone (P4) acting through the P4 receptor (PR) isoforms, PR-A and PR-B, promotes uterine quiescence for most of pregnancy, in part, by inhibiting the response of myometrial cells to pro-labor inflammatory stimuli. This anti-inflammatory effect is inhibited by phosphorylation of PR-A at serine-344 and -345 (pSer344/345-PRA). Activation of the cyclic adenosine monophosphate (cAMP) signaling pathway also promotes uterine quiescence and myometrial relaxation. ⋯ Forskolin inhibited pSer344/345-PRA generation, in part, by increasing the expression of dual specificity protein phosphatase 1 (DUSP1), a phosphatase that inactivates mitogen-activated protein kinases (MAPKs) including SAPK/JNK. P4/PR and forskolin increased DUSP1 expression. The data suggest that P4/PR promotes uterine quiescence via cross-talk and synergy with cAMP/PKA signaling in myometrial cells that involves DUSP1-mediated inhibition of SAPK/JNK activation.