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Keywords = phoenixin (PNX)

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24 pages, 3208 KiB  
Article
Distribution and Neurochemical Characterization of Dorsal Root Ganglia (DRG) Neurons Containing Phoenixin (PNX) and Supplying the Porcine Urinary Bladder
by Paweł Janikiewicz, Urszula Mazur, Piotr Holak, Nastassia Karakina, Kamil Węglarz, Mariusz Krzysztof Majewski and Agnieszka Bossowska
Cells 2025, 14(7), 516; https://doi.org/10.3390/cells14070516 - 31 Mar 2025
Viewed by 494
Abstract
The present study was designed to establish the distribution pattern and immunohistochemical characteristics of phoenixin-immunoreactive (PNX-IR) urinary bladder afferent neurons (UB-ANs) of dorsal root ganglia (DRG) in female pigs. The sensory neurons investigated were visualized with a retrograde tracing method using Fast Blue [...] Read more.
The present study was designed to establish the distribution pattern and immunohistochemical characteristics of phoenixin-immunoreactive (PNX-IR) urinary bladder afferent neurons (UB-ANs) of dorsal root ganglia (DRG) in female pigs. The sensory neurons investigated were visualized with a retrograde tracing method using Fast Blue (FB), while their chemical profile(s) were identified using double-labelling immunohistochemistry with antibodies against PNX, calcitonin gene-related peptide (CGRP), calretinin (CRT), galanin (GAL), neuronal nitric oxide synthase (nNOS), pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin (SOM) and substance P (SP). Nearly half of UB-ANs contained PNX (45%), and the majority of such encoded sensory neurons were small in size (66%). The most numerous subpopulation of FB/PNX-positive neurons were those containing SP (71%). CGRP, GAL or PACAP were observed in a smaller number of PNX-containing UB-ANs (50%, 30% or 25%, respectively), while PNX-positive sensory neurons simultaneously immunostained with nNOS, CRT or SOM constituted a small fraction of all retrogradely-traced DRG neurons (DRGs; 15%, 6.5% or 1.6%, respectively). Furthermore, the numerical analysis of neurons expressing individual antigens, performed on 10 μm-thick consecutive sections, allows us to state that studied sensory neurons can be classified as neurons “coded” either by the simultaneous presence of SP/CGRP/PACAP/GAL, SP/CGRP/PACAP/NOS, SP/CGRP/PACAP/NOS/CRT and/or SP/CGRP/GAL/PACAP, or, as a separate population, those capable of SOM synthesis (SP/CGRP/SOM/PACAP/GAL-positive neurons). The present study reveals the extensive expression of PNX in the DRGs supplying to the urinary bladder, indicating an important regulatory role of this neuropeptide in the control of physiological function(s) of this organ. Full article
(This article belongs to the Section Cells of the Nervous System)
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15 pages, 2672 KiB  
Article
Potential Modulatory Role of Phoenixin-14 in Epithelial–Mesenchymal Transition of Endometriotic 12Z Cells
by Karolina Iwona Kulinska, Magdalena Wierzbicka, Anna Dera-Szymanowska, Krzysztof Szymanowski, Mirosław Andrusiewicz and Maria Wołuń-Cholewa
Biomedicines 2025, 13(1), 158; https://doi.org/10.3390/biomedicines13010158 - 10 Jan 2025
Viewed by 1180
Abstract
Background/Objectives: Endometriosis is a painful chronic condition in which the endometrium grows outside the uterus. The epithelial–mesenchymal transition (EMT) is critical to endometriosis progression, where cells lose epithelial traits and gain invasiveness. Methods: This study investigates the effects of phoenixin-14 (PNX-14), [...] Read more.
Background/Objectives: Endometriosis is a painful chronic condition in which the endometrium grows outside the uterus. The epithelial–mesenchymal transition (EMT) is critical to endometriosis progression, where cells lose epithelial traits and gain invasiveness. Methods: This study investigates the effects of phoenixin-14 (PNX-14), a neuropeptide found at reduced levels in endometriosis patients, on the expression of two molecular EMT markers, CDH1 (E-cadherin) and THBS2 (thrombospondin 2), as well as cell viability in the endometriosis-derived 12Z cell line. Cells were treated with physiological (0.2 nM) and endometriosis-relevant (0.05 nM) concentrations of PNX-14. Gene expression was analyzed using RT-qPCR, while protein localization was assessed by immunocytochemistry. Cell viability was measured using an XTT assay. Results: THBS2 gene expression was significantly decreased, and CDH1 remained unchanged in cells stimulated by 0.05 nM PNX-14. Immunolocalization indicates a weaker THBS2 and CDH1 protein immunosignal reaction for 0.05 nM PNX-14. PNX-14 treatment also exhibited a biphasic effect on cell viability. Lower concentration initially decreased viability at 48 h but then significantly increased it at 72 h. This increase coincided with the decrease in THBS2 expression, suggesting a potential link between PNX-14, THBS2, and cell viability. Conclusions: A negative correlation between cell viability and the expression of both EMT markers further highlights their possible involvement in the survival and adaptability of ectopic epithelial cells. Our findings suggest a complex interplay between PNX-14, EMT markers, and cell viability in ectopic epithelial cells. PNX-14’s ability to modulate these factors warrants further investigation to elucidate its role in endometriosis. Full article
(This article belongs to the Special Issue Molecular and Clinical Aspects of Endometriosis Pathophysiology)
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21 pages, 1192 KiB  
Review
Examining the Potential Applicability of Orexigenic and Anorexigenic Peptides in Veterinary Medicine for the Management of Obesity in Companion Animals
by Cezary Osiak-Wicha, Katarzyna Kras, Ewa Tomaszewska, Siemowit Muszyński and Marcin B. Arciszewski
Curr. Issues Mol. Biol. 2024, 46(7), 6725-6745; https://doi.org/10.3390/cimb46070401 - 1 Jul 2024
Cited by 2 | Viewed by 2402
Abstract
This review article comprehensively explores the role of orexigenic and anorexigenic peptides in the management of obesity in companion animals, with a focus on clinical applications. Obesity in domestic animals, particularly dogs and cats, is prevalent, with significant implications for their health and [...] Read more.
This review article comprehensively explores the role of orexigenic and anorexigenic peptides in the management of obesity in companion animals, with a focus on clinical applications. Obesity in domestic animals, particularly dogs and cats, is prevalent, with significant implications for their health and well-being. Factors contributing to obesity include overfeeding, poor-quality diet, lack of physical activity, and genetic predispositions. Despite the seriousness of this condition, it is often underestimated, with societal perceptions sometimes reinforcing unhealthy behaviors. Understanding the regulation of food intake and identifying factors affecting the function of food intake-related proteins are crucial in combating obesity. Dysregulations in these proteins, whether due to genetic mutations, enzymatic dysfunctions, or receptor abnormalities, can have profound health consequences. Molecular biology techniques play a pivotal role in elucidating these mechanisms, offering insights into potential therapeutic interventions. The review categorizes food intake-related proteins into anorexigenic peptides (inhibitors of food intake) and orexigenic peptides (enhancers of food intake). It thoroughly examines current research on regulating energy balance in companion animals, emphasizing the clinical application of various peptides, including ghrelin, phoenixin (PNX), asprosin, glucagon-like peptide 1 (GLP-1), leptin, and nesfatin-1, in veterinary obesity management. This comprehensive review aims to provide valuable insights into the complex interplay between peptides, energy balance regulation, and obesity in companion animals. It underscores the importance of targeted interventions and highlights the potential of peptide-based therapies in improving the health outcomes of obese pets. Full article
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25 pages, 3657 KiB  
Article
Distribution and Chemistry of Phoenixin-14, a Newly Discovered Sensory Transmission Molecule in Porcine Afferent Neurons
by Urszula Mazur, Ewa Lepiarczyk, Paweł Janikiewicz, Elżbieta Łopieńska-Biernat, Mariusz Krzysztof Majewski and Agnieszka Bossowska
Int. J. Mol. Sci. 2023, 24(23), 16647; https://doi.org/10.3390/ijms242316647 - 23 Nov 2023
Cited by 1 | Viewed by 1470
Abstract
Phoenixin-14 (PNX), initially discovered in the rat hypothalamus, was also detected in dorsal root ganglion (DRG) cells, where its involvement in the regulation of pain and/or itch sensation was suggested. However, there is a lack of data not only on its distribution in [...] Read more.
Phoenixin-14 (PNX), initially discovered in the rat hypothalamus, was also detected in dorsal root ganglion (DRG) cells, where its involvement in the regulation of pain and/or itch sensation was suggested. However, there is a lack of data not only on its distribution in DRGs along individual segments of the spinal cord, but also on the pattern(s) of its co-occurrence with other sensory neurotransmitters. To fill the above-mentioned gap and expand our knowledge about the occurrence of PNX in mammalian species other than rodents, this study examined (i) the pattern(s) of PNX occurrence in DRG neurons of subsequent neuromeres along the porcine spinal cord, (ii) their intraganglionic distribution and (iii) the pattern(s) of PNX co-occurrence with other biologically active agents. PNX was found in approximately 20% of all nerve cells of each DRG examined; the largest subpopulation of PNX-positive (PNX+) cells were small-diameter neurons, accounting for 74% of all PNX-positive neurons found. PNX+ neurons also co-contained calcitonin gene-related peptide (CGRP; 96.1%), substance P (SP; 88.5%), nitric oxide synthase (nNOS; 52.1%), galanin (GAL; 20.7%), calretinin (CRT; 10%), pituitary adenylate cyclase-activating polypeptide (PACAP; 7.4%), cocaine and amphetamine related transcript (CART; 5.1%) or somatostatin (SOM; 4.7%). Although the exact function of PNX in DRGs is not yet known, the high degree of co-localization of this peptide with the main nociceptive transmitters SP and CGRP may suggests its function in modulation of pain transmission. Full article
(This article belongs to the Section Molecular Neurobiology)
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11 pages, 1225 KiB  
Article
Increased Serum Levels of Phoenixin-14, Nesfatin-1 and Dopamine Are Associated with Positive Pregnancy Rate after Ovarian Stimulation
by Magdalena Piróg, Robert Jach, Michał Ząbczyk and Joanna Natorska
J. Clin. Med. 2023, 12(22), 6991; https://doi.org/10.3390/jcm12226991 - 8 Nov 2023
Cited by 3 | Viewed by 1469
Abstract
Background: We study the relationship between phoenixin (PNX-14), nesfatin-1 (NES-1), dopamine (DA) and oxytocin (OT) levels together with pregnancy rates in women after ovarian stimulation (OS). Methods: In a prospective case–control study, 56 infertile women were enrolled from the Department of Gynecological Endocrinology [...] Read more.
Background: We study the relationship between phoenixin (PNX-14), nesfatin-1 (NES-1), dopamine (DA) and oxytocin (OT) levels together with pregnancy rates in women after ovarian stimulation (OS). Methods: In a prospective case–control study, 56 infertile women were enrolled from the Department of Gynecological Endocrinology University Hospital. Infertile women age < 40 years old, with polycystic ovary syndrome (PCOS), confirmed tubal patency and suitable sperm quality were included. Blood samples were drawn twice—before the initiation of OS and before the human chorionic gonadotropin (hCG) administration. Assessments of PNX-14, NES-1, DA and OT serum levels were performed. Pregnancy rates after OS were observed. Results: Pregnant women showed higher baseline NES-1 and OT levels (+29.2% and +44%) but not PNX-14 and DA levels when compared to non-pregnant ones. In pregnant women, positive correlations between OT and prolactin, PRL (r = 0.47, p = 0.04), as well as between OT and NES-1 (r = 0.55, p = 0.02), were observed at baseline. At baseline, an OT level increase was associated with a positive pregnancy rate (per 100 pg/mL, OR = 1.39, 95% CI 1.04–1.74), while after OS, higher PNX-14 was a predictor of pregnancy (by 10 pg/mL, OR = 1.23, 95%CI 1.07–1.39). Post-stimulation PNX-14, NES-1 and DA concentrations were higher in pregnant women compared to non-pregnant ones (+17.4%, +26.1%, and +45.5%, respectively; all p < 0.05). In the pregnant group, OT levels were 2.7-times lower than in the remainder (p = 0.03). Moreover, in pregnant participants, a negative association between NES-1 and PNX (r = −0.53, p = 0.024) was observed. Conclusion: Elevated PNX-14, NES-1 and DA along with decreased OT levels were observed in women who achieved pregnancy. Full article
(This article belongs to the Special Issue Reproductive Endocrinology and Infertility)
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11 pages, 6469 KiB  
Article
Exploring the Potential Link between Acute Central Serous Chorioretinopathy and Trimethylamine N-Oxide, Phoenixin, Spexin, and Alarin Molecules
by Mehmet Kaan Kaya and Sermal Arslan
Biomolecules 2023, 13(10), 1459; https://doi.org/10.3390/biom13101459 - 27 Sep 2023
Viewed by 1613
Abstract
Purpose: Acute central serous chorioretinopathy (ACSCR) is a condition characterized by decreased visual acuity, macular thickening, and edema under the retinal layer. Although the underlying mechanisms of the disease are not fully understood, oxidative stress is considered to be a critical risk factor. [...] Read more.
Purpose: Acute central serous chorioretinopathy (ACSCR) is a condition characterized by decreased visual acuity, macular thickening, and edema under the retinal layer. Although the underlying mechanisms of the disease are not fully understood, oxidative stress is considered to be a critical risk factor. The aim of this study was to shed light on the pathophysiology of ACSCR by investigating the levels of circulating trimethylamine N-oxide (TMAO), phoenixin (PNX), alarin (ALA), and spexin (SPX) molecules in ACSCR patients. Methods: The study included 30 ACSCR patients and 30 healthy individuals as controls. ACSCR was diagnosed using optical coherence tomography (OCT) imaging. Five mL blood samples were collected from all participants following overnight fasting. The levels of TMAO, PNX, ALA, and SPX in the blood samples were measured using the ELISA method. Results: Visual acuity was found to be significantly reduced in ACSCR patients compared to the control group (<0.05), while macular thickness was increased (<0.05). Furthermore, TMAO, PNX, and ALA levels were significantly higher in ACSCR patients (<0.05), while SPX levels were significantly lower compared to the control group (<0.05). In ACSCR patients, there was a positive correlation between macular thickness and TMAO, PNX, and ALA; there was, however, a negative correlation with SPX. Additionally, visual acuity was negatively correlated with TMAO, PNX, and ALA, while SPX levels decreased as visual acuity decreased. Conclusions: These results demonstrate a correlation between the TMAO, PNX, ALA, and SPX levels of ACSCR patients and their visual acuity and macular thickness. Given the role of these molecules in ACSCR’s pathophysiology, they hold promise as potential diagnostic, therapeutic, and follow-up markers in the future. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Retinal Degenerative Conditions)
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12 pages, 4957 KiB  
Article
Phoenixin as a New Target in the Development of Strategies for Endometriosis Diagnosis and Treatment
by Karolina Iwona Kulinska, Mirosław Andrusiewicz, Anna Dera-Szymanowska, Maria Billert, Marek Skrzypski, Krzysztof Szymanowski, Ewa Nowak-Markwitz, Małgorzata Kotwicka and Maria Wołuń-Cholewa
Biomedicines 2021, 9(10), 1427; https://doi.org/10.3390/biomedicines9101427 - 9 Oct 2021
Cited by 18 | Viewed by 2967
Abstract
Small integral membrane protein 20/phoenixin (SMIM20/PNX) and its receptor GPR173 (G Protein-Coupled Receptor 173) play a role in the regulation of the hypothalamic–pituitary–gonadal axis (HPG). The aim of the study was to determine PNX, FSH, LH, and 17β-estradiol association in women with endometriosis, [...] Read more.
Small integral membrane protein 20/phoenixin (SMIM20/PNX) and its receptor GPR173 (G Protein-Coupled Receptor 173) play a role in the regulation of the hypothalamic–pituitary–gonadal axis (HPG). The aim of the study was to determine PNX, FSH, LH, and 17β-estradiol association in women with endometriosis, and the expression of SMIM20/PNX signaling via GPR173. Serum PNX, FSH, LH, and 17β-estradiol concentrations were measured by enzyme and electrochemiluminescence immunoassay. SMIM20/PNX and GPR173 expression in the eutopic and ectopic endometrium was assessed by qPCR and immunohistochemistry. Reduced PNX level, increased LH/FSH ratio and elevated 17β-estradiol concentration were found in patients with endometriosis. No differences in SMIM20 expression were observed between the studied endometria. GPR173 expression was lower in ectopic than in eutopic endometria. SMIM20 expression was mainly restricted to stroma. GPR173 was detected in some eutopic and ectopic stromal cells and in eutopic glandular epithelial cells. Discriminant analysis indicates the diagnostic relevance of PNX and LH/FSH ratio in patients with endometriosis. In women with endometriosis, reduced PNX levels and GPR173 expression may be responsible for HPG axis dysregulation. These new insights may contribute to a better understanding of the pathophysiology of endometriosis and provide the basis for a new strategy for diagnosis and treatment of endometriosis. Full article
(This article belongs to the Special Issue Advanced Research in Endometriosis 2.0)
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15 pages, 1022 KiB  
Review
Phoenixin: More than Reproductive Peptide
by Maria Billert, Agnieszka Rak, Krzysztof W. Nowak and Marek Skrzypski
Int. J. Mol. Sci. 2020, 21(21), 8378; https://doi.org/10.3390/ijms21218378 - 8 Nov 2020
Cited by 46 | Viewed by 4869
Abstract
Phoenixin (PNX) neuropeptide is a cleaved product of the Smim20 protein. Its most common isoforms are the 14- and 20-amino acid peptides. The biological functions of PNX are mediated via the activation of the GPR173 receptor. PNX plays an important role in the [...] Read more.
Phoenixin (PNX) neuropeptide is a cleaved product of the Smim20 protein. Its most common isoforms are the 14- and 20-amino acid peptides. The biological functions of PNX are mediated via the activation of the GPR173 receptor. PNX plays an important role in the central nervous system (CNS) and in the female reproductive system where it potentiates LH secretion and controls the estrus cycle. Moreover, it stimulates oocyte maturation and increases the number of ovulated oocytes. Nevertheless, PNX not only regulates the reproduction system but also exerts anxiolytic, anti-inflammatory, and cell-protective effects. Furthermore, it is involved in behavior, food intake, sensory perception, memory, and energy metabolism. Outside the CNS, PNX exerts its effects on the heart, ovaries, adipose tissue, and pancreatic islets. This review presents all the currently available studies demonstrating the pleiotropic effects of PNX. Full article
(This article belongs to the Special Issue Peptides for Health Benefits 2020)
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