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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-cre(TM)-derived cardiac fibroblast progenitor (CFP)-specific PKR1 knockout mice (PKR1 (tcf-/-)), 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...
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...
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
F Guida, R Lattanzi, S Boccella, D Maftei, R Romano, V Marconi, G Balboni, S Salvadori, M A Scafuro, V de Novellis, L Negri, S Maione, L Luongo
Peripheral neuropathy is characterized by abnormal pain responses triggered by the release of several mediators and neuronal hyperexcitability at the spinal cord level. Emerging evidence indicates that the enhanced activity of dorsal horn neurons requires communication with glia and microglia, cells that are physiologically involved in neuronal wellbeing. Prokineticins (PKs), which include PK1 and PK2, represent a novel family of chemokines characterized by a unique structural motif comprising five disulfide bonds...
January 2015: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Takeshi Iwasa, Toshiya Matsuzaki, Altankhuu Tungalagsuvd, Munkhsaikhan Munkhzaya, Takako Kawami, Mikio Yamasaki, Masahiro Murakami, Takeshi Kato, Akira Kuwahara, Toshiyuki Yasui, Minoru Irahara
Prokineticin (PK2) and its receptors (PKRs) are expressed in several regions of the central nervous system, including the hypothalamus. It has been reported that PK2 inhibits food intake via PKR1 and that the hypothalamic PK2 mRNA levels of adult rodents were reduced by food deprivation. However, some hypothalamic factors do not exhibit sensitivity to undernutrition in the early neonatal period, but subsequently become sensitive to it during the neonatal to pre-pubertal period. In this study, we investigated the changes in the sensitivity of hypothalamic PK2 and PKR1 mRNA expression to fasting during the developmental period in male rats...
November 2014: International Journal of Developmental Neuroscience
D Maftei, V Marconi, F Florenzano, L A Giancotti, M Castelli, S Moretti, E Borsani, L F Rodella, G Balboni, L Luongo, S Maione, P Sacerdote, L Negri, R Lattanzi
BACKGROUND AND PURPOSE: Chemokines are involved in neuroinflammation and contribute to chronic pain processing. The new chemokine prokineticin 2 (PROK2) and its receptors (PKR1 and PKR2 ) have a role in inflammatory pain and immunomodulation. In the present study, we investigated the involvement of PROK2 and its receptors in neuropathic pain. EXPERIMENTAL APPROACH: Effects of single, intrathecal, perineural and s.c. injections of the PKR antagonist PC1, or of 1 week s...
November 2014: British Journal of Pharmacology
Wenqing Yin, Huadie Liu, Zhen Peng, Danna Chen, Jie Li, Jia-Da Li
Prokineticins (PKs) are a pair of signal factors involved in many physiological processes by binding to two closely related G-protein-coupled receptors (GPCRs), PKR1 and PKR2. We recently demonstrated that PKR2 undergoes rapid ligand-induced endocytosis, and PKR2 recycles back to the plasma membrane after the removal of ligand. However, little is known about the molecular mechanisms underlying the PKR2 endocytosis. Here, we studied the involvement of GPCR kinase 2 (GRK2), β-arrestins, clathrin and protein kinase C (PKC) in the PKR2 endocytosis...
May 2014: Cellular Signalling
Cécilia Szatkowski, Judith Vallet, Mojdeh Dormishian, Nadia Messaddeq, Phillippe Valet, Mounia Boulberdaa, Daniel Metzger, Pierre Chambon, Canan G Nebigil
BACKGROUND: Adipocyte renewal from preadipocytes occurs throughout the lifetime and contributes to obesity. To date, little is known about the mechanisms that control preadipocyte proliferation and differentiation. Prokineticin-2 is an angiogenic and anorexigenic hormone that activate two G protein-coupled receptors (GPCRs): PKR1 and PKR2. Prokineticin-2 regulates food intake and energy metabolism via central mechanisms (PKR2). The peripheral effect of prokineticin-2 on adipocytes/preadipocytes has not been studied yet...
2013: PloS One
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