Receptors and clinical investigation最新文献

{"title":"Transient Receptor Potential Vanilloid 1 in animal tissues: An overview to highlight similarities and differences with human species","authors":"C. Vercelli, R. Barbero, G. Re","doi":"10.14800/RCI.646","DOIUrl":"https://doi.org/10.14800/RCI.646","url":null,"abstract":"The purpose of this review is to give an overview of the identification and the characterization of Transient Receptor Potential Vanilloid 1 (TRPV1) in animal tissues. TRPV1 is a receptor belonging to the superfamily of Transient Receptor potential (TRP) and it was first identified in dorsal root ganglion in 1997. After, the scientific interest on this receptor increased, and nowadays it is possible to read a huge bibliography dealing with this receptor that is considered ubiquitarian. Actually, it was identified in the majority of animal and human tissues in physiological and pathological conditions. The involvement of TRPV1 receptor is considered as a key to understand aetiopathogenic mechanisms and to try to find a therapeutic treatment. In spite of the deep knowledge on TRPV1 molecular structure, more studies are required to better understand the cascade following its activation. For all the previous mentioned reasons, TRPV1 was investigated in species of interest of Veterinary Medicine and some of them are important animal models for human medicine, especially for oncology and analgesic therapeutic strategies.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"13 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2015-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88312780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen receptor-dependent modulation of dendritic cell biology of mice and women","authors":"S. Laffont, J. Guéry","doi":"10.14800/RCI.671","DOIUrl":"https://doi.org/10.14800/RCI.671","url":null,"abstract":"Autoimmune and infectious diseases differentially affect women from men. Women tend to develop stronger immune responses and thus in general men are more susceptible to infectious diseases whereas women are more likely to develop autoimmune diseases. These differences could be in part attributable to the pro-inflammatory role of the female sex hormone estrogen on immunity and particularly on dendritic cells (DCs), a key subset of innate immune cells. For several years now, we have undertaken studies to understand how estrogens influence the biology of murine and human DCs. We and others have demonstrated that estradiol (E2) was required for the optimal in vitro differentiation of murine DCs and acquisition of their effector functions. These effects on DC biology were dependent on the activation of the estrogen receptor a (ERa). More recently, we focused our interest on plasmacytoid dendritic cells (pDCs). Indeed, this subset that produces large amounts of IFN-a/b in response to viral or endogenous nucleic acids through activation of their TLR-7 and TLR-9 show gender differences with enhanced IFN-a production by pDCs from women, compared to men. We could establish, in Human and in mice, that in vivo treatment with E2 enhanced the TLR-dependent production of IFNa by pDCs. In mice, we demonstrated that the amplifying effect of endogenous and exogenous estrogens is dependent on the intrinsic activation of ERα by hormone in the pDCs. To further characterize the mechanisms underlying this sex-based difference in pDC innate functions, we investigated the respective contribution of X chromosome dosage versus sex hormones using a humanized mouse model in which male or female NOD-SCID-s2m -/- mice were transplanted with human progenitor cells (HPCs) purified from either male (XY) or female (XX) donors. We could show that cell-intrinsic ER-signaling and X chromosome complement both independently contribute to the enhanced TLR-7-mediated response of pDCs in women, which may account for the sex-based differences in autoimmune and infectious diseases. Altogether, our work demonstrates that estrogen-mediated activation of ER signaling is a key regulator of DC biology both in Human and in mouse.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81735159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPR30 is a potential therapeutic target in human carcinoma in situ and seminomas","authors":"P. Chieffi","doi":"10.14800/RCI.676","DOIUrl":"https://doi.org/10.14800/RCI.676","url":null,"abstract":"The G protein-coupled estrogen receptor (GPR30) is suggested to exert a role in non-nuclear estrogen signalling and is over-expressed in a variety of hormone dependent cancer entities. It is well established that oestrogens are involved in testicular germ cell tumours. In a recent paper published in Journal of Cellular Physiology, we show that down regulation of estrogen receptor β (ERβ) associates with GPR30 over-expression both in human testicular carcinoma in situ (CIS) and seminomas. In addition, we demonstrate that 17b-oestradiol induces the ERK1/2 activation through GPR30. The results suggested that exposure to oestrogens or oestrogen-mimics, in some as of yet undefined manner, diminishes the ERb-mediated growth restraint in CIS and in human testicular seminoma, indicating that GPR30 could be a potential therapeutic target to design specific inhibitors.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75944996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spry2 is a novel therapeutic target for periodontal tissue regeneration through fibroblast growth factor receptor signaling and epidermal growth factor signaling","authors":"T. Sanui, T. Fukuda, Urara Tanaka, Kyosuke Toyoda, Takaharu Taketomi, F. Nishimura","doi":"10.14800/RCI.597","DOIUrl":"https://doi.org/10.14800/RCI.597","url":null,"abstract":"Sprouty2 (Spry2) inhibits the activation of the extracellular signal-regulated kinase (ERK) pathway via receptor tyrosine kinase signaling. In a recent paper published in Journal of Cellular Biochemistry, we demonstrated that transfection of a dominant-negative mutant of Spry2 enhanced fibroblast growth factor (FGF)- and epidermal growth factor (EGF)-induced ERK activation in osteoblasts. In contrast, it decreased their activation in gingival epithelial cells. Consistent with these observations, the sequestration of Spry2 increased osteoblast proliferation by FGFR and EGFR stimulation, whereas it decreased gingival epithelial cell proliferation via the ubiquitination and degradation of EGF receptors (EGFR). In addition, reduction of Spry2 activity upregulated Runx2 expression and downregulated Twist, a negative regulator of Runx2 through FGFR and EGFR signaling, resulting in enhanced osteoblastogenesis in osteoblasts. Furthermore, we also found that suppression of Spry2 upregulated cell proliferation and migration in human periodontal ligament cell lines when they were stimulated by both FGF and EGF, and led to a shift in macrophage polarization, exerted immunosuppressive and tissue-repairing effects in macrophages. These results suggest that the application of a Spry2 inhibitor may effectively resolve inflammation by periodontitis and allow periodontal ligament and alveolar bone to grow and block the ingrowth of gingival epithelial cells in bony defects, biologically mimicking the barrier effect seen in conventional GTR. This approach has potential for developing a new regeneration strategy.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74329972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Membrane stretch and angiotensin II type 1a receptor: causes and role in the myogenic response","authors":"J. Tano, J. Schleifenbaum, M. Gollasch","doi":"10.14800/RCI.625","DOIUrl":"https://doi.org/10.14800/RCI.625","url":null,"abstract":"The ligand-independent activation of Angiotensin II type 1 receptors following vascular stretch plays very important (patho) physiological roles. Indeed, recent studies have implicated this mechanism in cardiac hypertrophy under conditions of pressure overload and it has shown to be indispensable in the regulation of the myogenic response in smooth muscle cells of small resistance arteries, as well as mesenteric and renal resistance arteries. The information discussed in here will highlight the involvement of the mechanoactivation of the Angiotensin II type I receptors in the development of the myogenic response and the molecular mechanisms modulating them following activation.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79093854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting receptor tyrosine kinases in malignant pleural mesothelioma: Focus on FGF-receptors","authors":"K. Schelch, M. Hoda, B. Hegedűs, B. Dome, W. Klepetko, W. Berger, M. Grusch","doi":"10.14800/RCI.543","DOIUrl":"https://doi.org/10.14800/RCI.543","url":null,"abstract":"Fibroblast growth factor receptors (FGFRs) constitute a subfamily of receptor tyrosine kinases. Four different receptors, FGFR1-4, bind 18 different fibroblast growth factors (FGFs) and signal mainly along the mitogen-activated protein kinase (MAPK), the phosphatidylinositol 3 kinase (PI3K) and the phospholipase c gamma (PLCγ) pathway. Physiologically, they are major regulators of embryonic development and metabolism. Deregulation of FGFR signals is increasingly recognized to play important roles in malignant diseases and may constitute a feasible therapeutic target. We recently investigated their role in malignant pleural mesothelioma (MPM), an aggressive malignancy mainly caused by asbestos exposure and with currently limited therapeutic options. We demonstrated high expression of several FGFs/FGFRs, especially FGFR1, FGF2 and FGF18 in cultured tumor cells and tissue specimens and identified FGFR-mediated signals as major driver of MPM cell growth, survival and migration. FGFR blockade by a tyrosine kinase inhibitor or by a dominant-negative receptor construct resulted in reduced MPM growth in vitro and in vivo and, furthermore, enhanced the efficacy of chemo- or radiotherapy. Several other receptor tyrosine kinases, including EGFR, MET and AXL were found to be overexpressed in MPM but translation into clinically successful therapeutic approaches has not yet been achieved. Inhibition of FGF-receptors may have the advantage of targeting both the tumor cells as well as the tumor vasculature and should be further evaluated.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"144 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76006460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Orexin regulates mitochondrial dynamics in avian muscle","authors":"E. Greene, K. Lassiter, W. Bottje, S. Dridi","doi":"10.14800/RCI.632","DOIUrl":"https://doi.org/10.14800/RCI.632","url":null,"abstract":"The growing obesity epidemic has sparked numerous studies on the identification of molecular signatures that regulate energy homeostasis using different experimental animal models. Orexin, which acts via two G-protein coupled receptors, orexin receptor 1 and 2, has been originally identified as feeding-related hypothalamic neuropeptide that regulate energy balance in mammals. Recently, using chicken, non-mammalian species that are characteristically hyperglycemic and prone to obesity, we made a breakthrough by identifying the orexin system in avian muscle and unraveling its effect on mitochondrial dynamics and function. Therefore, understanding orexin signaling and function may help to identify novel therapeutic opportunities for treating metabolic disorders related to mitochondrial dysfunction.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77301306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen pathway mutations and cancer","authors":"Ana Ferreira, R. Hofstra, H. Westers","doi":"10.14800/RCI.635","DOIUrl":"https://doi.org/10.14800/RCI.635","url":null,"abstract":"Cancer is caused by an accumulation of mutations in a stem cell. A defective mismatch repair (MMR) system can lead to such an accumulation of mutations. MMR defects are found in a cancer syndrome called Lynch Syndrome, and tumors of this syndrome are indeed characterized by such an accumulation of mutations, particularly in short repetitive DNA sequences, called microsatellites. When such mutated microsatellites are located in the coding sequences of genes with essential roles for tumorigenesis, we speak of ‘target genes’. Many such target genes have been found and in this review we focus the possible involvement of target genes involved in the estrogen-receptor pathway (ER). We recently identified NRIP1, encoding the nuclear receptor-interacting protein 1, as the most frequently mutated gene in microsatellite instable (MSI) endometrial cancer (EC). NRIP1 is a known corepressor of the ER pathway, the pathway essential in regulating the concentrations of estrogens, a hormone for which the endometrium is highly responsive. This in combination with the fact that high exposure to estrogens is currently considered the major risk factor for EC - approximately 80% of all sporadic EC tumors are estrogen dependent carcinomas - make NRIP1 the perfect target gene for EC. Interestingly, mutations in NRIP1 were also detected in MSI colorectal carcinoma (CRC) samples. Finding mutations in an estrogen receptor signaling protein in colorectal tissue might not be that expected, as colon is not typically associated with being responsive to estrogens. However, evidence is accumulating to better understand this finding. For instance, it was shown that NRIP1 , in colon tissue, stimulates APC gene transcription and inhibits β-catenin activation. Moreover, some studies suggested that estrogens can increase the expression of MLH1 in colon cancer cells, highlighting the implications of estrogen protecting against colon cancer, by regulating the MMR system. All in all we conclude that genes involved in the estrogen pathway are the perfect candidates to be studied in MMR-deficient tumors, especially those developing in hormonal responsive tissues.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"49 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80318278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Deltamethrin induced Immunotoxicity: Current and Future Perspectives","authors":"Anoop Kumar, A. Bhaskar, Saket Chandra, D. Sasmal, K. Mukhopadhyay, Neelima Sharma","doi":"10.14800/RCI.578","DOIUrl":"https://doi.org/10.14800/RCI.578","url":null,"abstract":"The immune system is the most vulnerable system regarding toxicity of pesticides. Any alteration in the immune functions makes an individual immunocompromised and more susceptible to cancer, infections, autoimmunity and allergies. Deltamethrin is the most popular type 2 pyrethroid insecticide which is widely use in agriculture and home due to restriction on the organophosphate insecticides. Due to their extensive use, it becomes an increasingly serious source of chemical pollution. We all are exposed to deltamethrin through inhalation, ingestion and dermal contact. It has been demonstrated that deltamethrin alters the immune response signalling pathways, but its mechanism of immunotoxicity is still an open question for researchers to be explored. Thus, herein we tried to understand the mechanism of deltamethrin induced immunotoxicity. Possibilities of deltamethrin induced other immunotoxic signalling pathways have also been discussed and should be considered in future studies. Further, current challenges and future perspectives have been also discussed.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73581133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen Receptor (AR) and Breast Cancer: Reference to the AR Status in Normal/Benign Breast Luminal Cells","authors":"Xi Wang","doi":"10.14800/RCI.533","DOIUrl":"https://doi.org/10.14800/RCI.533","url":null,"abstract":"The role of androgen and androgen receptor pathway in breast cancer development, prognosis and treatment has gained enormous attentions in recent years, largely because of the effort to identify new markers for targeted treatment of triple (ER/PR/Her2) negative breast carcinomas. This mini-review will discuss AR and breast cancer from the perspectives of normal/benign breast luminal epithelium.","PeriodicalId":20980,"journal":{"name":"Receptors and clinical investigation","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88464809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}