• Development and Reproduction
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• v.16 no.2
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• pp.121-128
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• 2012

Kisspeptin has been reported to facilitate sexual maturation and ovulation by directly stimulating GnRH neurons via its receptor, GPR54. The KiSS-GPR54 system is playing an important role in the reproduction of several mammalian species. However, little is known about their function in fish. The aim of this study is to understand the physiological function and evolutionary conservation of KiSS-GPR54 system in teleost fish blacktip grouper, Epinephelus fasciatus. In the present study, we have partial cloned KiSS1, KiSS2 GPR54 mRNAs from a brain samples. Tissue distribution analysis using RT-PCR revealed that the KiSS1, KiSS2, GPR54 transcripts were expressed in different tissue. The KiSS-GPR54 system in gonadal of immature and mature stage were analyzed using qRT-PCR. The partial sequence of KiSS1, KiSS2, GPR54 were 232 bp, 304 bp, 613 bp long, respectively. KiSS1, KiSS2, GPR54 mRNAs are shown common expression in the brain. The amount of KiSS1, KiSS2 mRNAs expression were significantly higher in mature stage than immature stage. However GPR54 mRNA expression was higher in immature stage. These results are in good agreement with the hypothesis that KiSS-GPR54 system plays an important role in the regulation of reproductive function in the blacktip grouper.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1789-1795
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• 2016

Background: Breast cancer is the commonest female cancer worldwide and its propensity to metastasize negatively impacts on therapeutic outcome. Several clinicopathological parameters with prognostic/predictive significance have been associated with metastatic suppressor expression levels. The role of metastatic suppressor gene (MSG) KiSS1 in breast cancer remains unclear. Our goal was to investigate the possible clinical significance of KiSS1 breast cancer. Materials and Methods: The study was conducted on 87 histologically proven cases of breast cancer and background normal tiisue. Quantitative reverse transcriptase polymerase chain reaction (qRT PCR) and immunohistochemistry (IHC) were used to investigate KiSS1 at gene and protein levels, respectively, for correlation with several patient characteristics including age, family history, hormonal receptor status, stage, tumor size, nodal involvement and metastatic manifestation and finally with median overall survival (OS). Results: Our study revealed (i) KiSS1 levels were generally elevated in breast cancer vs normal tissue (P < 0.05). (ii) however, a statistically significant lower expression of KiSS1 was observed in metastatic vs non metastatic cases (P = 0.04). (iii) KiSS1 levels strongly correlated with T,N,M category, histological grade and advanced stage (p<0.001) but not other studied parameters. (iv) Lastly, a significant correlation between expression of KiSS1 and median OS was found (P = 0.04). Conclusions: Conclusively, less elevated KiSS1 expression is a negative prognostic factor for OS, advancing tumor stage, axillary lymph node status, metastatic propensity and advancing grade of the breast cancer patient. Patients with negative KiSS1 expression may require a more intensive therapeutic strategy.

• Molecules and Cells
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• v.45 no.12
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• pp.935-949
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• 2022

Liver cancer has a high prevalence, with majority of the cases presenting as hepatocellular carcinoma (HCC). The prognosis of metastatic HCC has hardly improved over the past decade, highlighting the necessity for liver cancer research. Studies have reported the ability of the KiSS1 gene to inhibit the growth or metastasis of liver cancer, but contradictory research results are also emerging. We, therefore, sought to investigate the effects of KiSS1 on growth and migration in human HCC cells. HepG2 human HCC cells were infected with lentivirus particles containing KiSS1. The overexpression of KiSS1 resulted in an increased proliferation rate of HCC cells. Quantitative polymerase chain reaction and immunoblotting revealed increased Akt activity, and downregulation of the G1/S phase cell cycle inhibitors. A significant increase in tumor spheroid formation with upregulation of β-catenin and CD133 was also observed. KiSS1 overexpression promoted the migratory, invasive ability, and metastatic capacity of the hepatocarcinoma cell line, and these effects were associated with changes in the expressions of epithelial mesenchymal transition (EMT)- related genes such as E-cadherin, N-cadherin, and slug. KiSS1 overexpression also resulted in dramatically increased tumor growth in the xenograft mouse model, and upregulation of proliferating cell nuclear antigen (PCNA) and Ki-67 in the HCC tumors. Furthermore, KiSS1 increased the angiogenic capacity by upregulation of the vascular endothelial growth factor A (VEGF-A) and CD31. Based on these observations, we infer that KiSS1 not only induces HCC proliferation, but also increases the metastatic potential by increasing the migratory ability and angiogenic capacity.

• Clinical and Experimental Pediatrics
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• v.55 no.9
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• pp.337-343
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• 2012

Purpose: Leptin has been considered a link between metabolic state and reproductive activity. Defective reproductive function can occur in leptin-deficient and leptin-excessive conditions. The aim of this study was to examine the effects of centrally injected leptin on the hypothalamic KiSS-1 system in relation to gonadotropin-releasing hormone (GnRH) action in the initial stage of puberty. Methods: Leptin (1 ${\mu}g$) was injected directly into the ventricle of pubertal female mice. The resultant gene expressions of hypothalamic GnRH and KiSS-1 and pituitary LH, 2 and 4 hours after injection, were compared with those of saline-injected control mice. The changes in the gene expressions after blocking the GnRH action were also analyzed. Results: The basal expression levels of KiSS-1, GnRH, and LH were significantly higher in the pubertal mice than in the prepubertal mice. The 1-${\mu}g$ leptin dose significantly decreased the mRNA expression levels of KiSS-1, GnRH, and LH in the pubertal mice. A GnRH antagonist significantly increased the KiSS-1 and GnRH mRNA expression levels, and the additional leptin injection decreased the gene expression levels compared with those in the control group. Conclusion: The excess leptin might have suppressed the central reproductive axis in the pubertal mice by inhibiting the KiSS-1 expression, and this mechanism is independent of the GnRH-LH-estradiol feedback loop.

• Development and Reproduction
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• v.9 no.1
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• pp.1-5
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• 2005

The hypothalamo-pituitary-gonadal hormone axis is centrally controlled by a complex regulatory network of excitatory and inhibitory signals, that is dormant during infantile and juvenile periods and activated at puberty. The kisspeptins are the peptide products of the KiSS-1 gene and the endogenous agonists for the G protein-coupled receptor 54(GPR54). Although KiSS-1 was initially discovered as a metastasis suppressor gene, a recent evidence suggests the KiSS-1/GPR54 system is a key regulator of the reproductive system. Yet the actual role of the KiSS-1/GPR54 system in the neuroendocrine control of gonadotropin secretion remains largely unexplored, the system could be the first missing link in the reproductive hormonal axis. Central or peripheral administration of kisspeptin stimulates the hypothalamic-pituitary-gonadal axis, increasing circulating gonadotropin levels in rodents, sheep, monkey and human models. These effects appear likely to be mediated via the hypothalamic GnRH neuron system, although kisspeptins may have direct effects on the anterior pituitary gland. The loss of function mutations of the GPR54(GPR54-/-) have been associated with lack of puberty onset and idiopathic hypogonadotropic hypogonadism(IHH). So kisspeptin infusion may provide a novel mechanism for HPG axis manipulation in disorders of the reproductive system.

• Journal of Integrative Natural Science
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• v.9 no.2
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• pp.136-143
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• 2016

KiSS1-derived peptide receptor, a GPCR protein, binds with the hormone kiss peptin. They are important in the neuroendocrine regulation of reproduction and in the secretion of gonadotrophin-releasing hormone. Thus, analysing the structural features of the receptor becomes important. However, the three dimensional structure of the protein is unavailable. Hence in this study, we have performed the homology modelling of KiSS1-derived peptide receptor with 5 different templates. 30 models were constructed using two platforms - Easymodeller and ITasser. The optimal models were chosen based on the model validation. Two models were selected after validation. The developed models could provide useful for analysing the structural features of KiSS1-derived peptide receptor and their pathophysiological role in various disorders related to them.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6215-6220
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• 2013

Kisspeptins (KPs) encoded by the KiSS-1 gene are C-terminally amidated peptide products, including KP-10, KP-13, KP-14 and KP-54, which are endogenous agonists for the G-protein coupled receptor-54 (GPR54). Functional analyses have demonstrated fundamental roles of KiSS-1 in whole body homeostasis including sexual differentiation of brain, action on sex steroids and metabolic regulation of fertility essential for human puberty and maintenance of adult reproduction. In addition, intensive recent investigations have provided substantial evidence suggesting roles of Kisspeptin signalling via its receptor GPR54 in the suppression of metastasis with a variety of cancers. The present review highlights the latest studies regarding the role of Kisspeptins and the KiSS-1 gene in tumor progression and also suggests targeting the KiSS-1/GPR54 system may represent a novel therapeutic approach for cancers. Further investigations are essential to elucidate the complex pathways regulated by the Kisspeptins and how these pathways might be involved in the suppression of metastasis across a range of cancers.

• Journal of Integrative Natural Science
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• v.11 no.1
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• pp.9-13
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• 2018

KiSS1-derived peptide receptor, a GPCR protein, binds with the hormone Kisspeptin plays a major role in the neuroendocrine regulation of reproduction. It is important in the onset of puberty and triggers the release of gonadotrophin-releasing hormone. It is a potential drug target for the disorders related to GnRH, hence, analysing the structural features of the receptor becomes important. The three dimensional of the receptor modelled in a previous study was utilised. In this study, we have analysed the protein - protein interaction of the receptor with Kisspeptin 10 and 15. The study revealed the important residues which are involved in the interaction. The result of this study could be helpful in understanding the mechanism of Kiss1 receptor activation and the pathophysiology of the disorders related to the receptor.

• Journal of Industrial Technology
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• v.27 no.B
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• pp.83-89
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• 2007

We studied runoff characteristics of combined sewer overflows in a city while it was raining. The event mean concentration (EMC) of biochemical oxygen demand (BOD), chemical oxygen demand ($COD_{Cr}$), suspended solids (SS), total nitrogen (TN), and total phosphorus (TP) in one of the combined sewer sites in Chuncheon was 63.5-211.6 mg/L, 114.9-523.8 mg/L, 70.3-436.4 mg/L, 6.4-33.0 mg/L, and 1.09-6.81 mg/L, respectively. In another combined sewer, the EMC of BOD, COD, SS, TN, and TP was 42.1-131.4 mg/L, 107.7-256.5 mg/L, 33.7-221.1 mg/L, 7.9-26.4 mg/L, and 1.16-3.91 mg/L, respectively. The ratio of the cumulative pollutant mass and the cumulative discharged volume determined using all parameters (BOD, $COD_{Cr}$, SS, TN, and TP) was over 1.0, which shows the first flush effect. Relationships between flow and loadings of BOD, $COD_{Cr}$, SS, TN, and TP were 0.90, 0.89, 0.88, 0.89, 0.92, respectively. Although the size of two areas was almost same, pollutant concentration and loading were different because of the amount of rainfall, rainfall intensity and basin area.

• IMMUNE NETWORK
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• v.20 no.5
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• pp.39.1-39.13
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• 2020

Sjögren's syndrome (SS) is a chronic and systemic autoimmune disease characterized by lymphocytic infiltration in the exocrine glands. In SS, type I IFN has a pathogenic role, and recently, inflammasome activation has been observed in both immune and non-immune cells. However, the relationship between type I IFN and inflammasome-associated pyroptosis in SS has not been studied. We measured IL-18, caspase-1, and IFN-stimulated gene 15 (ISG15) in saliva and serum, and compared whether the expression levels of inflammasome and pyroptosis components, including absent in melanoma 2 (AIM2), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and gasdermin E (GSDME), in minor salivary gland (MSG) are related to the expression levels of type I IFN signature genes. Expression of type I IFN signature genes was correlated with mRNA levels of caspase-1 and GSDMD in MSG. In confocal analysis, the expression of caspase-1 and GSDMD was higher in salivary gland epithelial cells (SGECs) from SS patients. In the type I IFN-treated human salivary gland epithelial cell line, the expression of caspase-1 and GSDMD was increased, and pyroptosis was accelerated in a caspase-dependent manner upon inflammasome activation. In conclusion, we demonstrate that type I IFN may contribute to inflammasome-associated pyroptosis of the SGECs of SS patients, suggesting another pathogenic role of type I IFN in SS in terms of target tissue -SGECs destruction.