Phoenixin—A Pleiotropic Gut-Brain Peptide

Schalla, Martha A.; Stengel, Andreas

doi:10.3390/ijms19061726

Cited by 27 publications

(23 citation statements)

References 48 publications

(127 reference statements)

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“…Moreover, it has also been reported that there is a significant positive correlation of plasma PNX and nesfatin‐1 levels in women affected by polycystic ovarian syndrome (Ullah et al, ). Both PNX (Schalla & Stengel, ) and nesfatin‐1 (Pan, Hsuchou, & Kastin, ) can cross a relatively impermeable blood–brain barrier. Therefore, it is presumed that higher plasma PNX and nesfatin‐1 levels in polycystic ovarian syndrome patients could reach hypothalamus or pituitary cells and affect the GnRH‐dependent HPGA.…”

Section: Discussionmentioning

confidence: 99%

Contingent role of phoenixin and nesfatin‐1 on secretions of the male reproductive hormones

et al. 2019

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Phoenixin (PNX) and nesfatin‐1 are localised in the hypothalamus and the pituitary gland. Moreover, the most of the PNX‐expressing neurons in the hypothalamus also co‐express nesfatin‐1. These outcomes may suggest that there is an interaction between PNX and nesfatin‐1, at least in terms of neuroendocrine‐mediated regulations. Hence, the study was planned to find out the effects of centrally delivered PNX and nesfatin‐1 on male sex hormones or to show the interactive association of intracerebroventricularly (ICV) injected PNX+nesfatin‐1 combination on the release of male hormones. PNX and nesfatin‐1, single or together, were delivered ICV to different male Wistar Albino rat groups. Both PNX and nesfatin‐1 induced a significant enhancement in plasma FSH, LH and testosterone without inducing any alteration in plasma GnRH in the rats. The central combinatorial treatment of both the neuropeptides produced a more potent rise in male plasma hormone levels than treating with single neuropeptide. In summary, our preliminary data show that centrally delivered PNX and nesfatin‐1 can affect plasma male hormone levels. Moreover, that the combinatorial treatment with both the neuropeptides in male rats leading to a more potent effect on the plasma male hormone levels might suggest that both these neuropeptides act synergistically in terms of regulation of male HPGA.

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Section: Discussionmentioning

confidence: 99%

Contingent role of phoenixin and nesfatin‐1 on secretions of the male reproductive hormones

et al. 2019

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“…Within the hypothalamus, phoenixin and GPR173 are found to be expressed in multiple regions related to reproductive control including the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Despite extensive characterization of phoenixin in other peripheral tissues (Prinz et al 2017, Schalla & Stengel 2018, Stein et al 2018, the potential existence of phoenixin and GPR173 in human gonads, and particularly their possible role in human GC regulation has not been discovered yet.…”

Section: Introductionmentioning

confidence: 99%

Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis

Nguyen¹,

Nakamura²,

Osuka³

et al. 2019

Reproduction

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Folliculogenesis is a complex process, defined by the growth and development of follicles from the primordial population. Granulosa cells (GCs) play a vital role in every stage of follicular growth through proliferation, acquisition of gonadotropic responsiveness, steroidogenesis and production of autocrine/paracrine factors. A recently discovered hypothalamic neuropeptide phoenixin is involved in the regulation of the reproductive system. Phoenixin acts through its receptor, G protein-coupled receptor 173 (GPR173), to activate the cAMP/PKA pathway leading to the phosphorylation of CREB (pCREB). Here, we demonstrated the expression patterns of phoenixin and GPR173 in human ovary and explored its role in folliculogenesis. Phoenixin and GPR173 were both expressed in the human ovarian follicle, with increased expression in GCs as the follicle grows. Phoenixin treatment at 100 nM for 24 h induced the proliferation of human non-luteinized granulosa cell line, HGrC1 and significantly increased the expression levels of CYP19A1, FSHR, LHR and KITL, but decreased NPPC expression levels. These effects were suppressed by GPR173 siRNA. The expression level of CREB1, pCREB and estradiol (E2) production in the culture medium was significantly enhanced by phoenixin treatment in a concentration-dependent manner. Phoenixin also significantly increased the follicular area in a murine ovarian tissue culture model, leading to an increased number of ovulated oocytes with a higher level of maturation. Taken together, our data demonstrate that phoenixin is an intraovarian factor that promotes follicular growth through its receptor GPR173 by accelerating proliferation of GCs, inducing E2 production and increasing the expression of genes related to follicle development.

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“…The pleiotropic peptide phoenixin 20 is part of the C4orf52 C-terminus family and is found in a diverse range of species, with few variations. Currently, phoenixin 20 is recognized as having a possible link to a range of bene cial effects, such as reduced anxiety and improved memory, as well as a role in the gut-brain axis [2]. Through its wide-ranging effects and impressive potential to ameliorate various aspects of disease, we identi ed this protein as a possible treatment for atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Phoenixin-20 Prevents ox-LDL-Induced Attachment of Monocytes to Human Aortic Endothelial Cells (HAECs): A Protective Implication in Atherosclerosis

Wei

Lin

Zhang

et al. 2021

ACS Chem. Neurosci.

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Background: The cause of atherosclerosis is not known, and therefore the current treatment options are limited. In the present study, we aimed to investigate the effects of Phoenixin 20 and its receptor G protein-coupled receptor 173 (GPR173) against ox-LDL-induced endothelial dysfunction.Materials and Methods: Human aortic endothelial cells (HAECs) were treated with 10 μg/ml ox-LDL in the presence or absence of phoenixin 20. Gene expression of GPR173, ICAM-1, VCAM-1, IL-1β, IL-8, MCP-1, and NOX-4 were measured by real time PCR. Protein expression was assayed by western blot analysis. Secretions of pro-in ammatory cytokines were measured by ELISA. The attachment of THP-1 monocytes to HAECs was detected using calcein-AM staining. Transcriptional activity of NF-κB was measured using dual-luciferase reporter assay.Results: Our ndings indicate that ox-LDL signi cantly lowered the expression of GPR173 in HAECs and triggered an increase in ROS, NOX-4, and proin ammatory cytokine expression. Importantly, we demonstrate that agonism of GPR173 using phoenixin 20 signi cantly ameliorated these harmful effects of ox-LDL. We also show that agonism of GPR173 can prevent the attachment of monocytes to endothelial cells, which is an important therapeutic approach to prevent atherogenesis. Conclusion:Here, for the rst time to our knowledge, we provide a basis for future research on the role of GPR173 as a new potential treatment against atherosclerosis.

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Phoenixin—A Pleiotropic Gut-Brain Peptide

Cited by 27 publications

References 48 publications

Contingent role of phoenixin and nesfatin‐1 on secretions of the male reproductive hormones

Contingent role of phoenixin and nesfatin‐1 on secretions of the male reproductive hormones

Effect of the neuropeptide phoenixin and its receptor GPR173 during folliculogenesis

Phoenixin-20 Prevents ox-LDL-Induced Attachment of Monocytes to Human Aortic Endothelial Cells (HAECs): A Protective Implication in Atherosclerosis

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