scholarly journals Cionin, a vertebrate cholecystokinin/gastrin homolog, induces ovulation in the ascidian Ciona intestinalis type A

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tomohiro Osugi ◽  
Natsuko Miyasaka ◽  
Akira Shiraishi ◽  
Shin Matsubara ◽  
Honoo Satake
Keyword(s):  
Gene Expression ◽  
Receptor Tyrosine Kinase ◽  
Ciona Intestinalis ◽  
Type A ◽  
Phylogenetic Position ◽  
Rtk Signaling ◽  
Mmp Inhibitor ◽  
Ovulatory Follicles

AbstractCionin is a homolog of vertebrate cholecystokinin/gastrin that has been identified in the ascidian Ciona intestinalis type A. The phylogenetic position of ascidians as the closest living relatives of vertebrates suggests that cionin can provide clues to the evolution of endocrine/neuroendocrine systems throughout chordates. Here, we show the biological role of cionin in the regulation of ovulation. In situ hybridization demonstrated that the mRNA of the cionin receptor, Cior2, was expressed specifically in the inner follicular cells of pre-ovulatory follicles in the Ciona ovary. Cionin was found to significantly stimulate ovulation after 24-h incubation. Transcriptome and subsequent Real-time PCR analyses confirmed that the expression levels of receptor tyrosine kinase (RTK) signaling genes and a matrix metalloproteinase (MMP) gene were significantly elevated in the cionin-treated follicles. Of particular interest is that an RTK inhibitor and MMP inhibitor markedly suppressed the stimulatory effect of cionin on ovulation. Furthermore, inhibition of RTK signaling reduced the MMP gene expression in the cionin-treated follicles. These results provide evidence that cionin induces ovulation by stimulating MMP gene expression via the RTK signaling pathway. This is the first report on the endogenous roles of cionin and the induction of ovulation by cholecystokinin/gastrin family peptides in an organism.

scholarly journals Cionin, A Vertebrate Cholecystokinin/Gastrin Homolog, Induces Ovulation in the Ascidian Ciona Intestinalis Type A.

2021 ◽  
Author(s):  
Tomohiro Osugi ◽  
Natsuko Miyasaka ◽  
Akira Shiraishi ◽  
Shin Matsubara ◽  
Honoo Satake
Keyword(s):  
Gene Expression ◽  
Receptor Tyrosine Kinase ◽  
Ciona Intestinalis ◽  
Type A ◽  
Phylogenetic Position ◽  
Rtk Signaling ◽  
Mmp Inhibitor ◽  
Ovulatory Follicles

Abstract Cionin is a homolog of vertebrate cholecystokinin/gastrin that has been identified in the ascidian Ciona intestinalis type A. The phylogenetic position of ascidians as the closest living relatives of vertebrates suggests that cionin can provide clues to the evolution of endocrine/neuroendocrine systems throughout chordates. Here, we show the biological role of cionin in the regulation of ovulation. In situ hybridization demonstrated that the mRNA of the cionin receptor, Cior2, was expressed specifically in the inner follicular cells of pre-ovulatory follicles in the Ciona ovary. Cionin was found to significantly stimulate ovulation after 24-h incubation. Transcriptome and subsequent Real-time PCR analyses confirmed that the expression levels of receptor tyrosine kinase (RTK) signaling genes and a matrix metalloproteinase (MMP) gene were significantly elevated in the cionin-treated follicles. Of particular interest is that an RTK inhibitor and MMP inhibitor markedly suppressed the stimulatory effect of cionin on ovulation. Furthermore, inhibition of RTK signaling reduced the MMP gene expression in the cionin-treated follicles. These results provide evidence that cionin induces ovulation by stimulating MMP gene expression via the RTK signaling pathway. This is the first report on the endogenous roles of cionin and the induction of ovulation by cholecystokinin/gastrin family peptides in an organism.

scholarly journals Capicua controls Toll/IL-1 signaling targets independently of RTK regulation

2018 ◽  
Vol 115 (8) ◽  
pp. 1807-1812 ◽  
Author(s):  
Aikaterini Papagianni ◽  
Marta Forés ◽  
Wanqing Shao ◽  
Shuonan He ◽  
Nina Koenecke ◽  
...  
Keyword(s):  
Gene Expression ◽  
Receptor Tyrosine Kinase ◽  
Binding Sites ◽  
Regulatory Mechanisms ◽  
Cooperative Binding ◽  
Affinity Binding ◽  
Lower Affinity ◽  
Rtk Signaling ◽  
Enhancer Regulation

The HMG-box protein Capicua (Cic) is a conserved transcriptional repressor that functions downstream of receptor tyrosine kinase (RTK) signaling pathways in a relatively simple switch: In the absence of signaling, Cic represses RTK-responsive genes by binding to nearly invariant sites in DNA, whereas activation of RTK signaling down-regulates Cic activity, leading to derepression of its targets. This mechanism controls gene expression in both Drosophila and mammals, but whether Cic can also function via other regulatory mechanisms remains unknown. Here, we characterize an RTK-independent role of Cic in regulating spatially restricted expression of Toll/IL-1 signaling targets in Drosophila embryogenesis. We show that Cic represses those targets by binding to suboptimal DNA sites of lower affinity than its known consensus sites. This binding depends on Dorsal/NF-κB, which translocates into the nucleus upon Toll activation and binds next to the Cic sites. As a result, Cic binds to and represses Toll targets only in regions with nuclear Dorsal. These results reveal a mode of Cic regulation unrelated to the well-established RTK/Cic depression axis and implicate cooperative binding in conjunction with low-affinity binding sites as an important mechanism of enhancer regulation. Given that Cic plays a role in many developmental and pathological processes in mammals, our results raise the possibility that some of these Cic functions are independent of RTK regulation and may depend on cofactor-assisted DNA binding.

Proteinase-activated receptors in ovine cervical function

2005 ◽  
Vol 17 (7) ◽  
pp. 693 ◽  
Author(s):  
Sharon E. Mitchell ◽  
John J. Robinson ◽  
Margaret E. King ◽  
Lynda M. Williams
Keyword(s):  
Gene Expression ◽  
In Situ Hybridisation ◽  
Prostaglandin F2α ◽  
Cervical Dilation ◽  
Proteinase Activated Receptors ◽  
Pregnant Ewe ◽  
High Level ◽  
And Function

In sheep, inflammation not only functions in cervical dilation at parturition, but also plays an important part in the non-pregnant ewe cervix, as demonstrated by the high level of expression of interleukin (IL)-8 at oestrus. Ewes artificially induced to ovulate have significantly lower levels of IL-8 gene expression at oestrus compared with natural oestrus, indicating an inhibition of inflammation and function, offering an explanation for the low rates of conception in vaginally inseminated synchronised ewes. To identify potential pro-inflammatory agents to combat the anti-inflammatory effects of hormonal synchronisation of oestrus, we have investigated the role of proteinase-activated receptor (PAR)-1 and PAR-2. To localise and measure the level of expression of these receptors, ovine-specific probes were derived for PAR-1 and PAR-2 and used for quantitative in situ hybridisation in the ovine cervix. Both PAR-1 and PAR-2 were expressed in the luminal epithelium of the cervix throughout the oestrous cycle, with expression being highest at oestrus. The gene expression of PAR-2 at oestrus was approximately 30% higher than that of PAR-1. Artificial synchronisation of oestrus by either an intravaginal progesterone sponge or prostaglandin F2α injections did not inhibit PAR-1 or PAR-2 expression at oestrus; rather, in the case of PAR-2, progesterone synchronisation increased it. Both synchronising procedures increased the expression of PAR-1 and PAR-2 during the luteal phase of the cycle. Therefore, agonists of PAR-1 and PAR-2 may be potentially useful pro-inflammatory agents countering the inhibition of inflammation by hormonal synchronisation.

scholarly journals Ascending Brainstem Pathways Are Not Involved in Lipopolysaccharide-Induced Suppression of Thyrotropin-Releasing Hormone Gene Expression in the Hypothalamic Paraventricular Nucleus

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1357-1363 ◽  
Author(s):  
Csaba Fekete ◽  
Praful S. Singru ◽  
Sumit Sarkar ◽  
William M. Rand ◽  
Ronald M. Lechan
Keyword(s):  
Gene Expression ◽  
Paraventricular Nucleus ◽  
Hypothalamic Paraventricular Nucleus ◽  
Nonthyroidal Illness ◽  
Intact Side ◽  
In Situ Hybridization Histochemistry ◽  
Immunocytochemical Detection ◽  
Lps Treatment

The nonthyroidal illness syndrome associated with fasting, infection, and chronic illness is characterized by low thyroid hormone levels and low or inappropriately normal TSH levels in circulating blood and reduced synthesis of TRH in hypophysiotropic neurons residing in the hypothalamic paraventricular nucleus (PVN). To test the hypothesis that ascending brainstem pathways are involved in mediation of bacterial lipopolysaccharide (LPS)-induced suppression of TRH mRNA in the PVN, we unilaterally transected brainstem pathways to the PVN and determined the effects of LPS on TRH gene expression and, as a control, on CRH gene expression in hypophysiotropic neurons using semiquantitative in situ hybridization histochemistry. The efficacy of the transection was determined by immunocytochemical detection of ascending adrenergic pathways in the PVN. In vehicle-treated animals, CRH mRNA in the PVN showed a significant reduction on the transected side compared with the intact side, whereas a significant increase in TRH mRNA was observed on the transected side compared with the intact side. After LPS administration (250 μg/100 g body weight), a dramatic increase in CRH mRNA was observed on the intact side, and a significantly lesser increase was found on the transected side. In contrast, LPS treatment resulted in reduction in TRH mRNA on the transected side compared with the intact side and a significant reduction in TRH mRNA on the transected side compared with vehicle-treated animals. These studies confirm an important role of ascending brainstem projections in LPS-induced activation of CRH gene expression, but indicate that they do not mediate the effect of LPS to inhibit hypophysiotropic TRH gene expression.

scholarly journals A Novel Biological Role of Tachykinins as an Up-Regulator of Oocyte Growth: Identification of an Evolutionary Origin of Tachykininergic Functions in the Ovary of the Ascidian, Ciona intestinalis

Endocrinology ◽  
2008 ◽  
Vol 149 (9) ◽  
pp. 4346-4356 ◽  
Author(s):  
Masato Aoyama ◽  
Tsuyoshi Kawada ◽  
Manabu Fujie ◽  
Kohji Hotta ◽  
Tsubasa Sakai ◽  
...  
Keyword(s):  
Gene Expression ◽  
Regulation Of Gene Expression ◽  
Model Organism ◽  
Ciona Intestinalis ◽  
Enzymatic Activities ◽  
Evolutionary Origin ◽  
Phylogenetic Position ◽  
Specific Expression ◽  
Oocyte Growth ◽  
Vitellogenic Stage

Tachykinins (TKs) and their receptors have been shown to be expressed in the mammalian ovary. However, the biological roles of ovarian TKs have yet to be verified. Ci-TK-I and Ci-TK-R, characterized from the protochordate (ascidian), Ciona intestinalis, are prototypes of vertebrate TKs and their receptors. In the present study, we show a novel biological function of TKs as an inducible factor for oocyte growth using C. intestinalis as a model organism. Immunostaining demonstrated the specific expression of Ci-TK-R in test cells residing in oocytes at the vitellogenic stage. DNA microarray and real-time PCR revealed that Ci-TK-I induced gene expression of several proteases, including cathepsin D, chymotrypsin, and carboxy-peptidase B1, in the ovary. The enzymatic activities of these proteases in the ovary were also shown to be enhanced by Ci-TK-I. Of particular significance is that the treatment of Ciona oocytes with Ci-TK-I resulted in progression of growth from the vitellogenic stage to the post-vitellogenic stage. The Ci-TK-I-induced oocyte growth was blocked by a TK antagonist or by protease inhibitors. These results led to the conclusion that Ci-TK-I enhances growth of the vitellogenic oocytes via up-regulation of gene expression and enzymatic activities of the proteases. This is the first clarification of the biological roles of TKs in the ovary and the underlying essential molecular mechanism. Furthermore, considering the phylogenetic position of ascidians as basal chordates, we suggest that the novel TK-regulated oocyte growth is an “evolutionary origin” of the tachykininergic functions in the ovary.

Lipopolysaccharide reduces gonadotrophin-releasing hormone (GnRH) gene expression: role of RFamide-related peptide-3 and kisspeptin

2019 ◽  
Vol 31 (6) ◽  
pp. 1134 ◽  
Author(s):  
Chooi Yeng Lee ◽  
ShengYun Li ◽  
Xiao Feng Li ◽  
Daniel A. E. Stalker ◽  
Claire Cooke ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Situ Hybridisation ◽  
Releasing Hormone ◽  
Related Peptide ◽  
Concomitant Reduction ◽  
Intracerebroventricular Injections ◽  
Gonadotrophin Releasing Hormone ◽  
Lh Secretion

RFamide-related peptide (RFRP)-3 reduces luteinising hormone (LH) secretion in rodents. Stress has been shown to upregulate the expression of the RFRP gene (Rfrp) with a concomitant reduction in LH secretion, but an effect on expression of the gonadotrophin-releasing hormone (GnRH) gene (Gnrh1) has not been shown. We hypothesised that lipopolysaccharide (LPS)-induced stress affects expression of Rfrp, the gene for kisspeptin (Kiss1) and/or Gnrh1, leading to suppression of LH levels in rats. Intracerebroventricular injections of RFRP-3 (0.1, 1, 5 nmol) or i.v. LPS (15μgkg−1) reduced LH levels. Doses of 1 and 5 nmol RFRP-3 were then administered to analyse gene expression by in situ hybridisation. RFRP-3 (5 nmol) had no effect on Gnrh1 or Kiss1 expression. LPS stress reduced GnRH and Kiss1 expression, without affecting Rfrp1 expression. These data indicate that LPS stress directly or indirectly reduces Gnrh1 expression, but this is unlikely to be due to a change in Rfrp1 expression.

scholarly journals miR-146a modulates TLR1/2 and 4 induced inflammation and links it with proliferation and lipid production via the indirect regulation of GNG7 in human SZ95 sebocytes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katalin Dull ◽  
Fruzsina Fazekas ◽  
Dávid Deák ◽  
Dóra Kovács ◽  
Szilárd Póliska ◽  
...  
Keyword(s):  
Gene Expression ◽  
In Situ Hybridization ◽  
Gene Expression Profile ◽  
Lipid Content ◽  
Lipid Production ◽  
Sebaceous Glands ◽  
Down Regulation ◽  
Protein Coding

AbstractActivation of Toll-like receptors (TLR) 1/2 and 4 are central in inducing inflammation in sebocytes by regulating the expression of protein coding mRNAs, however the microRNA (miRNA) profile in response to TLR activation and thus the possible role of miRNAs in modulating sebocyte functions has not been elucidated. In this work we identified miR-146a to have the highest induction in the TLR1/2 and 4 activated SZ95 sebocytes and found that its increased levels led to the down-regulation of IL-8 secretion, decreased the chemoattractant potential and stimulated the proliferation of sebocytes. Assessing the gene expression profile of SZ95 sebocytes treated with a miR-146a inhibitor, the induction of GNG7 was one of the highest, while when cells were treated with a miR-146a mimic, the expression of GNG7 was down-regulated. These findings correlated with our in situ hybridization results, that compared with control, miR-146a showed an increased, while GNG7 a decreased expression in sebaceous glands of acne samples. Further studies revealed, that when inhibiting the levels of GNG7 in SZ95 sebocytes, cells increased their lipid content and decreased their proliferation. Our findings suggest, that miR-146a could be a potential player in acne pathogenesis by regulating inflammation, inducing proliferation and, through the indirect down-regulation of GNG7, promoting the lipid production of sebocytes.

scholarly journals High-resolution targeted 3C interrogation of cis-regulatory element organization at genome-wide scale

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Damien J. Downes ◽  
Robert A. Beagrie ◽  
Matthew E. Gosden ◽  
Jelena Telenius ◽  
Stephanie J. Carpenter ◽  
...  
Keyword(s):  
Gene Expression ◽  
High Resolution ◽  
Regulatory Element ◽  
Gene Promoters ◽  
Entire Genome ◽  
Chromosome Conformation ◽  
Genome Wide ◽  
Wide Scale

AbstractChromosome conformation capture (3C) provides an adaptable tool for studying diverse biological questions. Current 3C methods generally provide either low-resolution interaction profiles across the entire genome, or high-resolution interaction profiles at limited numbers of loci. Due to technical limitations, generation of reproducible high-resolution interaction profiles has not been achieved at genome-wide scale. Here, to overcome this barrier, we systematically test each step of 3C and report two improvements over current methods. We show that up to 30% of reporter events generated using the popular in situ 3C method arise from ligations between two individual nuclei, but this noise can be almost entirely eliminated by isolating intact nuclei after ligation. Using Nuclear-Titrated Capture-C, we generate reproducible high-resolution genome-wide 3C interaction profiles by targeting 8055 gene promoters in erythroid cells. By pairing high-resolution 3C interaction calls with nascent gene expression we interrogate the role of promoter hubs and super-enhancers in gene regulation.

scholarly journals Quantitative Phosphoproteomics Reveals System-Wide Phosphorylation Network Altered by Spry in Mouse Mammary Stromal Fibroblasts

2019 ◽  
Vol 20 (21) ◽  
pp. 5400 ◽  
Author(s):  
Tiezhu Shi ◽  
Linli Yao ◽  
Ying Han ◽  
Piliang Hao ◽  
Pengfei Lu
Keyword(s):  
Cancer Progression ◽  
Receptor Tyrosine Kinase ◽  
Normal Development ◽  
Underlying Mechanism ◽  
Phosphorylation Sites ◽  
Additional Insight ◽  
Stromal Fibroblasts ◽  
Rtk Signaling ◽  
Insight Into

Understanding the fundamental role of the stroma in normal development and cancer progression has been an emerging focus in recent years. The receptor tyrosine kinase (RTK) signaling pathway has been reported playing critical roles in regulating the normal and cancer microenvironment, but the underlying mechanism is still not very clear. By applying the quantitative phosphoproteomic analysis of Sprouty proteins (SPRYs), generic modulators of RTK signaling and deleted mouse mammary fibroblasts, we quantified a total of 11,215 unique phosphorylation sites. By contrast, 554 phosphorylation sites on 425 proteins had SPRY-responsive perturbations. Of these, 554 phosphosites, 362 sites on 277 proteins, were significantly increased, whereas 192 sites on 167 proteins were decreased. Among the regulated proteins, we identified 31 kinases, 7 phosphatases, and one phosphatase inhibitor that were not systematically characterized before. Furthermore, we reconstructed a phosphorylation network centered on RTK signaling regulated by SPRY. Collectively, this study uncovered a system-wide phosphorylation network regulated by SPRY, providing an additional insight into the complicated RTK signaling pathways involved in the mammary gland microenvironment.

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