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Rehana Qureshi, Michel Kindo, Mounia Boulberdaa, Jean-Jacques von Hunolstein, Marja Steenman, Canan G Nebigil
Epicardial adipose tissues (EAT) and vascular tissues may both belong to the mesoepithelial lineage that develops from epicardium-derived progenitor cells (EPDCs) in developing and injured hearts. Very little is known of the molecular mechanisms of EPDC contribution in EAT development and neovascularization in adult heart, which the topic remains a subject of intense therapeutic interest and scientific debate. Here we studied the epigenetic control of stemness and anti-adipogenic and pro-vasculogenic fate of hEPDCs, through investigating an angiogenic hormone, prokineticin-2 (PK2) signaling via its receptor PKR1...
June 6, 2018: Stem Cells
Haixia Li, Jingtao Wang, Pengqian Wang, Yingying Zhang, Jun Liu, Yanan Yu, Bing Li, Zhong Wang
Recent evidence demonstrates that a double dose of Jasminoidin (2·JA) is more effective than Jasminoidin (JA) in cerebral ischemia therapy, but its dosage-effect mechanisms are unclear. In this study, the software GeneGo MetaCore was used to perform pathway analysis of the differentially expressed genes obtained in microarrays of mice belonging to four groups (Sham, Vehicle, JA, and 2·JA), aiming to elucidate differences in JA and 2·JA's dose-dependent pharmacological mechanism from a system's perspective...
2018: BioMed Research International
Benjamin Hommel, Liliane Mukaremera, Radames J B Cordero, Carolina Coelho, Christopher A Desjardins, Aude Sturny-Leclère, Guilhem Janbon, John R Perfect, James A Fraser, Arturo Casadevall, Christina A Cuomo, Françoise Dromer, Kirsten Nielsen, Alexandre Alanio
The pathogenic fungus Cryptococcus neoformans exhibits morphological changes in cell size during lung infection, producing both typical size 5 to 7 μm cells and large titan cells (> 10 μm and up to 100 μm). We found and optimized in vitro conditions that produce titan cells in order to identify the ancestry of titan cells, the environmental determinants, and the key gene regulators of titan cell formation. Titan cells generated in vitro harbor the main characteristics of titan cells produced in vivo including their large cell size (>10 μm), polyploidy with a single nucleus, large vacuole, dense capsule, and thick cell wall...
May 2018: PLoS Pathogens
Lucia Negri, Napoleone Ferrara
The mammalian prokineticins family comprises two conserved proteins, EG-VEGF/PROK1 and Bv8/PROK2, and their two highly related G protein-coupled receptors, PKR1 and PKR2. This signaling system has been linked to several important biological functions, including gastrointestinal tract motility, regulation of circadian rhythms, neurogenesis, angiogenesis and cancer progression, hematopoiesis, and nociception. Mutations in PKR2 or Bv8/PROK2 have been associated with Kallmann syndrome, a developmental disorder characterized by defective olfactory bulb neurogenesis, impaired development of gonadotropin-releasing hormone neurons, and infertility...
April 1, 2018: Physiological Reviews
Ying Li, Jiaojiao Wang, Lili Yu, Kai Zhao, Biao Chen, Cuiling Li, Fan Yang, Hongfang Yuan, Huiping Zhang
PROBLEM: Prokineticin 2 (PK2), a pro-inflammatory peptide, is highly expressed in primary spermatocytes. However, systematic research on PK2 and testicular inflammation is lacking to date. METHOD OF STUDY: An experimental autoimmune orchitis (EAO) model was established to detect the expression of PK2 and its receptor (prokineticin receptor 1, PKR1) 50 and 80 days after immunization. PK2 siRNA sequence was injected into the rat rete testis to downregulate the expression of PK2...
June 2018: American Journal of Reproductive Immunology: AJRI
Rehana Qureshi, Michel Kindo, Himanshu Arora, Mounia Boulberdaa, Marja Steenman, Canan G Nebigil
Cardiac fat tissue volume and vascular dysfunction are strongly associated, accounting for overall body mass. Despite its pathophysiological significance, the origin and autocrine/paracrine pathways that regulate cardiac fat tissue and vascular network formation are unclear. We hypothesize that adipocytes and vasculogenic cells in adult mice hearts may share a common cardiac cells that could transform into adipocytes or vascular lineages, depending on the paracrine and autocrine stimuli. In this study utilizing transgenic mice overexpressing prokineticin receptor (PKR1) in cardiomyocytes, and tcf21ERT-creTM -derived cardiac fibroblast progenitor (CFP)-specific PKR1 knockout mice (PKR1tcf-/- ), as well as FACS-isolated CFPs, we showed that adipogenesis and vasculogenesis share a common CFPs originating from the tcf21+ epithelial lineage...
October 16, 2017: Scientific Reports
Alix A J Rouault, Abigail A Lee, Julien A Sebag
The Melanocortin Receptor Accessory Protein 2 (MRAP2) regulates the activity of several GPCRs involved in the control of food intake and energy expenditure. While MRAP2 was originally thought to exclusively interact with melanocortin receptors we have recently shown that it interacts with and inhibits the trafficking and signaling of the prokineticin receptor 1 (PKR1). In this study we demonstrate a new role of MRAP2 in the regulation of the orexin receptor 1 (OX1R) and identify the specific regions of MRAP2 required for the regulation of OX1R and PKR1...
December 2017: Biochimica et Biophysica Acta
Canan G Nebigil
Obesity is a fast growing epidemic event worldwide. Fatness is associated with a number of comorbidities, including cardiovascular diseases (CVDs). Although obesity can be heredity in 30-70% cases, the environmental contributions also play an important role in the increasing prevalence of obesity. The relationship between development of obesity and CVD is poorly characterized. Obesity and CVD can also be resulted from a common mechanism such as metabolic, inflammatory, and neurohormonal changes. Prokineticins are defined as cytokines (immunoregulatory proteins), adipokines (adipocyte-secreted hormone), angiogenic (increasing vessel formation), or aneroxic (lowering food intake) hormones...
2017: Frontiers in Cardiovascular Medicine
Manuela Zinni, Anna Rita Zuena, Veronica Marconi, Carla Petrella, Ilaria Fusco, Chiara Giuli, Nadia Canu, Cinzia Severini, Maria Broccardo, Vassilia Theodorou, Roberta Lattanzi, Paola Casolini
The early phase of life represents a critical period for the development of an organism. Interestingly, early life experiences are able to influence the development of the gastrointestinal tract and the reactivity to colonic inflammatory stress. We recently demonstrated that adult male rats exposed to low doses of corticosterone during lactation (CORT-nursed rats) are protected against experimental colitis induced by the intracolonic infusion of 2,4,6-trinitrobenzenesulfonic acid (TNBS). Based on these interesting results, we wanted to better investigate which cellular actors could be involved in the protection of CORT-nursed rats from TNBS-induced experimental colitis...
2017: PloS One
Haruyasu Ito, Kentaro Noda, Ken Yoshida, Kazuhiro Otani, Masayuki Yoshiga, Yohsuke Oto, Saburo Saito, Daitaro Kurosaka
BACKGROUND: Prokineticin 2 (PK2) expression is upregulated in mice with collagen-induced arthritis (CIA), an animal model of rheumatoid arthritis. The purpose of our study was to investigate the effects of PK2 inhibition on CIA. METHODS: PK2, prokineticin receptor (PKR) 1, and PKR2 mRNA transcripts in the joints of CIA mice were measured by real-time PCR on Days 21, 28, and 35 (n = 15/day). Localization of PKR1 and PKR2 proteins was examined immunohistochemically...
September 8, 2016: BMC Musculoskeletal Disorders
Himanshu Arora, Mounia Boulberdaa, Rehana Qureshi, Verda Bitirim, Adeline Gasser, Nadia Messaddeq, Pascal Dolle, Canan G Nebigil
The epicardium plays an essential role in coronary artery formation and myocardial development. However, signals controlling the developing epicardium and epicardial-mesenchymal transition (EMT) in the normal and diseased adult heart are studied less rigorously. Here we investigated the role of angiogenic hormone, prokineticin-2 and its receptor PKR1 in the epicardium of developing and adult heart. Genetic ablation of PKR1 in epicardium leads to partial embryonic and postnatal lethality with abnormal heart development...
May 6, 2016: Scientific Reports
Elisa Landucci, Roberta Lattanzi, Elisabetta Gerace, Tania Scartabelli, Gianfranco Balboni, Lucia Negri, Domenico E Pellegrini-Giampietro
Bv8/prokineticin 2 (PK2) is a member of a bioactive family of peptides that regulate multiple functions in the CNS including hyperalgesia, neurogenesis, neuronal survival and inflammation. Recent studies have associated PK2 and prokineticin receptors (PKR) with human diseases, but because their role in neuropathology is still debated we examined whether prokineticins exert a protective or deleterious role in models of cerebral ischemia and ischemic tolerance in vitro. In order to mimic cerebral ischemia, we exposed primary murine cortical cell cultures or rat organotypic hippocampal slices to appropriate periods of oxygen-glucose deprivation (OGD), which leads to neuronal damage 24 h later...
September 2016: Neuropharmacology
Himanshu Arora, Mounia Boulberdaa, Rehana Qureshi, Verda Bitirim, Nadia Messadeq, Pascal Dolle, Canan G Nebigil
Identification of factors regulating renal development is important to understand the pathogenesis of congenital kidney diseases. Little is known about the molecular mechanism of renal development and functions triggered by the angiogenic hormone prokineticin-2 and its receptor, PKR1. Utilizing the Gata5 (G5)-Cre and Wilms tumor 1 (Wt1)(GFP)cre transgenic lines, we generated mutant mice with targeted PKR1 gene disruptions in nephron progenitors. These mutant mice exhibited partial embryonic and postnatal lethality...
August 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Yun-lei Cao, Zhao-feng Zhang, Jian Wang, Mao-hua Miao, Jian-hua Xu, Yue-ping Shen, Ai-min Chen, Jing Du, Wei Yuan
Recurrent pregnancy loss (RPL) is a condition with complex etiologies, to which both genetic and environmental factors may contribute. During the last decade, studies indicated that the expression patterns of the prokineticin receptor (PKR1 and PKR2) are closely related to early pregnancy. However, there are few studies on the role of PKR1 and PKR2 in RPL. In this study, we purpose to investigate the association between polymorphisms of the prokineticin receptor (PKR1 rs4627609 and PKR2 rs6053283) and RPL on a group of 93 RPL cases and 169 healthy controls...
March 2016: Journal of Zhejiang University. Science. B
Anna L Chaly, Dollada Srisai, Ellen E Gardner, Julien A Sebag
The Melanocortin Receptor Accessory Protein 2 (MRAP2) is an important regulator of energy homeostasis and its loss causes severe obesity in rodents. MRAP2 mediates its action in part through the potentiation of the MC4R, however, it is clear that MRAP2 is expressed in tissues that do not express MC4R, and that the deletion of MRAP2 does not recapitulate the phenotype of Mc4r KO mice. Consequently, we hypothesized that other GPCRs involved in the control of energy homeostasis are likely to be regulated by MRAP2...
February 1, 2016: ELife
Biao Chen, Lili Yu, Jiaojiao Wang, Cuiling Li, Kai Zhao, Huiping Zhang
Prokineticin 2, a newly discovered proinflammatory peptide, has been amply evidenced to be involved in the occurrence and progress of local and systematical inflammation. Although the presence of Prokineticn 2 in mammal testis has been documented clearly, research targeting the involvement of prokineticin 2 in testicular pathology, especially testitis, is rather scarce. Employing a lipopolysaccharide-induced testitis rat model, we for the first time demonstrated the expression and upregulation of prokineticin 2 in orchitis at several levels...
April 2016: Inflammation
Dorothee Heck, Sebastian Wortmann, Luitgard Kraus, Cristina L Ronchi, Richard O Sinnott, Martin Fassnacht, Silviu Sbiera
Angiogenesis is essential for tumor growth and metastasis. Endocrine gland-derived vascular endothelial growth factor (EG-VEGF) is an angiogenic factor predominantly expressed in steroidogenic organs like the adrenal gland, ovary, testes, and placenta. EG-VEGF has antiapoptotic, mitogenic, and chemoattractive properties mediated via the two G protein-coupled receptors prokineticin receptor 1 (PKR1) and prokineticin receptor 2 (PKR2). We investigated the expression of EG-VEGF and its receptors in a large number of normal adrenal glands (NAG), adrenocortical adenomas (ACA), and carcinomas (ACC) using real-time PCR (NAG, n = 12; ACA, n = 24; and ACC, n = 30) and immunohistochemistry (NAG, n = 9; ACA, n = 23; and ACC, n = 163) and evaluated its impact on patients' survival...
December 2015: Hormones & Cancer
Jean-Jacques Von Hunolstein, Canan G Nebigil
PURPOSE OF REVIEW: Because of its increasing prevalence and morbi-mortality, obesity is a major health problem. Obesity etiology includes a combination of excess dietary calories and decreased physical activity, coupled with either predisposing genetic factors or metabolic disorders such as insulin resistance. Adipose tissue secretes several metabolically important proteins known as 'adipokines' that play a major role in obesity and insulin resistance. High levels of a newly identified group of adipokines, called prokineticins, have been found in obese adipose tissues...
October 2015: Current Opinion in Endocrinology, Diabetes, and Obesity
Adeline Gasser, Simone Brogi, Kyoji Urayama, Toshishide Nishi, Hitoshi Kurose, Andrea Tafi, Nigel Ribeiro, Laurent Désaubry, Canan G Nebigil
Prokineticins are angiogenic hormones that activate two G protein-coupled receptors: PKR1 and PKR2. PKR1 has emerged as a critical mediator of cardiovascular homeostasis and cardioprotection. Identification of non-peptide PKR1 agonists that contribute to myocardial repair and collateral vessel growth hold promises for treatment of heart diseases. Through a combination of in silico studies, medicinal chemistry, and pharmacological profiling approaches, we designed, synthesized, and characterized the first PKR1 agonists, demonstrating their cardioprotective activity against myocardial infarction (MI) in mice...
2015: PloS One
Roberta Lattanzi, Daniela Maftei, Veronica Marconi, Fulvio Florenzano, Silvia Franchi, Elisa Borsani, Luigi Fabrizio Rodella, Gianfranco Balboni, Severo Salvadori, Paola Sacerdote, Lucia Negri
The new chemokine Prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2) have a role in inflammatory pain and immunomodulation. Here we identified PROK2 as a critical mediator of neuropathic pain in the chronic constriction injury (CCI) of the sciatic nerve in mice and demonstrated that blocking the prokineticin receptors with two PKR1-preferring antagonists (PC1 and PC7) reduces pain and nerve damage. PROK2 mRNA expression was upregulated in the injured nerve since day 3 post injury (dpi) and in the ipsilateral DRG since 6 dpi...
2015: BioMed Research International
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