A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

Yang, Xiaoqing; Friedl, Andreas

doi:10.1007/978-3-319-12114-7_12

Cited by 26 publications

(9 citation statements)

References 135 publications

(162 reference statements)

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“…Indeed, acute injection of sRlx-HD augmented plasma levels of Prolactin significantly in WT-NP and CKO-NP mice. Moreover, we could show that sRlx-HD via Prolactin induces activation of the Prolactin major target signalling molecule STAT5 36 in LV tissue. Direct injection of Prolactin activated STAT5 in both genotypes further explaining how sRlx via Prolactin and STAT5 activation could induce cardiomyocyte growth in both genotypes.…”

Section: Discussionmentioning

confidence: 83%

Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart failure in experimental peripartum cardiomyopathy

et al. 2017

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AimsPeripartum cardiomyopathy (PPCM) is a systolic left ventricular dysfunction developing in the peripartum phase in previously healthy women. Relaxin-2 is a pregnancy hormone with potential beneficial effects in heart failure patients. We evaluated Relaxin-2 as a potential diagnostic marker and/or a therapeutic agent in PPCM.Methods and resultsIn healthy peripartum women, serum Relaxin-2 levels (measured by ELISA in the second half of pregnancy) were elevated showing a decreasing trend in the first postpartum week and returned to non-pregnant levels thereafter. In PPCM patients diagnosed in the first postpartum week, serum Relaxin-2 levels were lower compared to healthy postpartum stage-matched controls. In PPCM patients diagnosed later (0.5–10 months postpartum) Relaxin-2 levels were in the range of non-pregnant controls and not different from healthy postpartum stage-matched controls. In mice, serum Relaxin-1 (functional equivalent of human Relaxin-2) was increased late in pregnancy and rapidly cleared in the first postpartum week. In mice with PPCM due to a cardiomyocyte-specific knockout of STAT3 (CKO) neither low nor high dose of recombinant Relaxin-2 (serelaxin, sRlx-LD: 30 µg/kg/day; sRlx-HD: 300 µg/kg/day) affected cardiac fibrosis, inflammation and heart failure but sRlx-HD increased capillary/cardiomyocyte ratio. sRlx-HD significantly increased heart/body weight ratio and cardiomyocyte cross-sectional area in postpartum CKO and wild-type mice without changing the foetal gene expression program (ANP or β-MHC). sRlx-HD augmented plasma Prolactin levels in both genotypes, which induced cardiac activation of STAT5. In vitro analyses showed that Prolactin induces cardiomyocyte hypertrophy via activation of STAT5.ConclusionAlthough Relaxin-2 levels seemed lower in PPCM patients diagnosed early postpartum, we observed a high pregnancy-related variance of serum Relaxin-2 levels peripartum making it unsuitable as a biomarker for this condition. Supplementation with sRlx may contribute to angiogenesis and compensatory hypertrophy in the diseased heart, but the effects are not sufficient to prevent heart failure in an experimental PPCM model.

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Section: Discussionmentioning

confidence: 83%

Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart failure in experimental peripartum cardiomyopathy

et al. 2017

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“…In COMMD7 silenced HepG2 cells, the inhibition rate of NF-κB was 75%, suggesting that COMMD7 regulates the nuclear translocation of NF-κB and the consequent gene transcriptions involved in HCC growth [10]. However, it was demonstrated that mutational changes in individual proteins can cause fundamental functional changes well beyond the pathway they function in by a positive feedback loop embedded in the crosstalk [12–15]. Interestingly, many oncogenes associated with tumor development and progression are activated by NF-κB [16–18].…”

Section: Introductionmentioning

confidence: 99%

COMMD7 is correlated with a novel NF-κB positive feedback loop in hepatocellular carcinoma

et al. 2016

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The correlation between nuclear factor-kappa B (NF-κB) and COMMD7 in hepatocellular carcinoma (HCC) development remained unclear. Here, our clinicopathological data showed that COMMD7 is overexpressed in HCC with a correlation to NF-κB. Using HepG2 and SMMC-7721 cells that aberrantly overexpressed COMMD7, we found that NF-κB directly binds with COMMD7 promoter and serves as an activator for COMMD7 transcription by luciferase reporter assay, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA). In both HepG2 cells and SMMC-7721 cells, the silencing of COMMD7 significantly inhibited the cell proliferation, whereas NF-κB silencing inhibited the expression of COMMD7 and further inhibited cell proliferation. In addition, cell apoptosis was promoted by COMMD7 silencing, and further promoted by NF-κB silencing. Cell migration and invasion were also inhibited by COMMD7 silencing, and further inhibited by NF-κB silencing. Thus, COMMD7 is correlated with a novel NF-κB positive feedback loop in hepatocellular carcinoma. Developing strategies for the treatment of HCC should consider the correlation between NF-κB and COMMD7, so as to improve the specificity and sensitivity of therapy and to reduce toxicity.

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“…STATs are involved in a series of biological events, including cell differentiation 58 , angiogenesis 59 , innate immunity 60 and cell growth regulation 61 . Numerous studies have demonstrated that STAT3 is mainly expressed in glial cells 62 , 63 and is involved in inflammatory reactions 64 , 65 .…”

Section: Discussionmentioning

confidence: 99%

Molecular mechanisms underlying the involvement of the sigma-1 receptor in methamphetamine-mediated microglial polarization

Chao

Zhang

et al. 2017

Sci Rep

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Our previous study demonstrated that the sigma-1 receptor is involved in methamphetamine-induced microglial apoptosis and death; however, whether the sigma-1 receptor is involved in microglial activation as well as the molecular mechanisms underlying this process remains poorly understood. The aim of this study is to demonstrate the involvement of the sigma-1 receptor in methamphetamine-mediated microglial activation. The expression of σ-1R, iNOS, arginase and SOCS was examined by Western blot; activation of cell signaling pathways was detected by Western blot analysis. The role of σ-1R in microglial activation was further validated in C57BL/6 N WT and sigma-1 receptor knockout mice (male, 6–8 weeks) injected intraperitoneally with saline or methamphetamine (30 mg/kg) by Western blot combined with immunostaining specific for Iba-1. Treatment of cells with methamphetamine (150 μM) induced the expression of M1 markers (iNOS) with concomitant decreased the expression of M2 markers (Arginase) via its cognate sigma-1 receptor followed by ROS generation. Sequential activation of the downstream MAPK, Akt and STAT3 pathways resulted in microglial polarization. Blockade of sigma-1 receptor significantly inhibited the generation of ROS and activation of the MAPK and Akt pathways. These findings underscore the critical role of the sigma-1 receptor in methamphetamine-induced microglial activation.

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A Positive Feedback Loop Between Prolactin and Stat5 Promotes Angiogenesis

Cited by 26 publications

References 135 publications

Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart failure in experimental peripartum cardiomyopathy

Serelaxin treatment promotes adaptive hypertrophy but does not prevent heart failure in experimental peripartum cardiomyopathy

COMMD7 is correlated with a novel NF-κB positive feedback loop in hepatocellular carcinoma

Molecular mechanisms underlying the involvement of the sigma-1 receptor in methamphetamine-mediated microglial polarization

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