RESUMEN
OBJECTIVE: Semaphorin 4D (Sema4D) is a coupling factor expressed on osteoclasts that may hinder osteoblast differentiation. Since the leukocyte platelet-rich fibrin (L-PRF) membrane promotes growth factor concentration, this study aims to quantify the amount of Sema4D in L-PRF membranes, and analyze the impact of Sema4D on osteoblast cell function in vitro. DESIGN: Enzyme-linked immunosorbent assay (ELISA) was used to quantify the levels of Sema4D in both L-PRF and whole blood (serum). To analyze the impairment of Sema4D on osteoblasts, MC3T3-E1 cells were induced to osteogenic differentiation and exposed to Sema4D ranging from 10 to 500 ng/ml concentrations. The following parameters were assayed: 1) cell viability by MTT assay after 24, 48, and 72 h; 2) matrix mineralization by Alizarin Red staining after 14 days, 3) Runt-related transcription factor 2 (RUNX-2), osteocalcin (OCN), osteonectin (ONC), bone sialoprotein (BSP) and alkaline phosphatase (ALP) gene expression by qPCR. For all data, the significance level was set at 5%. RESULTS: The amount of Sema4D in the whole blood (serum) was higher than in L-PRF. Osteoblasts exposed to Sema4D at all tested concentrations exhibited a decrease in matrix mineralization formation as well in RUNX-2, OCN, ONC, BSP, and ALP gene expression (p < 0.05). CONCLUSION: The presence of Sema4D, a molecule known for suppressing osteoblast activity, diminishes within L-PRF, enhancing its ability to facilitate bone regeneration.
Asunto(s)
Fibrina Rica en Plaquetas , Semaforinas , Diferenciación Celular/genética , Leucocitos/metabolismo , Osteoblastos , Osteocalcina/metabolismo , Osteogénesis/genética , Fibrina Rica en Plaquetas/metabolismo , Semaforinas/farmacología , Semaforinas/metabolismo , Animales , RatonesRESUMEN
The aim of the present study was to evaluate the impact of SEMA4A genetic variants on expression of sema4A protein and its relation to autoimmunity development in Systemic Lupus Erythematosus and Rheumatoid Arthritis patients. A total of 541 SLE patients, 390 RA patients and 607 healthy individuals were genotyped. We also assessed SEMA4A mRNA expression from whole blood cells and the in vitro protein production from resting and activated T lymphocytes as well as mature dendritic cells from healthy individuals stratified according to their genotypes for SLE/RA associated SEMA4A variants. Our results showed that T/T genotype for rs3738581 SNP is associated with both RA and SLE development (p = .000053, OR = 2.35; p = .0019, OR = 2.07, respectively; statistical power = 100%) and also to an increased in vitro sema4A production in active T lymphocytes. Our findings are indicative of a T cell-specific upregulation of sema4A in the presence of T/T genotype, being a risk factor for SLE and RA.
Asunto(s)
Artritis Reumatoide/genética , Autoinmunidad/genética , Lupus Eritematoso Sistémico/genética , Semaforinas/genética , Linfocitos T/inmunología , Adulto , Anciano , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Brasil , Estudios de Casos y Controles , Estudios de Cohortes , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/inmunología , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , ARN Mensajero/análisis , ARN Mensajero/metabolismo , Semaforinas/metabolismo , Linfocitos T/metabolismo , Regulación hacia ArribaRESUMEN
PURPOSE: The semaphorins are related to angiogenesis and cell proliferation depending on the tissue. The purpose of this study was to assess gene expression of class 3 semaphorin (SEMA3A-F) and protein expression of semaphorin 3A (SEMA3A) within human endometrium throughout the menstrual cycle. METHODS: Gene expression of SEMA3A-F was analyzed by real-time PCR (qRT-PCR) and protein expression of SEMA3A was analyzed by ELISA in endometrial biopsies in the proliferative and secretory phase of the menstrual cycle. RESULTS: Gene expression of SEMA3A, SEMA3C, SEMA3D, and SEMA3E was statistically significant decreased in secretory compared to proliferative phase endometrium (p < 0.05). Accordingly, SEMA3A protein expression in the secretory phase was lower than protein expression in proliferative phase endometrium (p ≤ 0.05). CONCLUSION: SEMA3A, 3C, 3D, and 3E are possibly related to cell proliferation in the endometrium, being more expressed in the proliferative phase of the cycle. This finding may stimulate studies of class 3 semaphorins as a possible target for treatment of endometrial pathologies.
Asunto(s)
Proliferación Celular/genética , Endometrio/metabolismo , Ciclo Menstrual/metabolismo , Semaforinas/genética , Semaforinas/metabolismo , Biopsia , Endometrio/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Glicoproteínas de Membrana , Proteínas de la Membrana , Proteínas del Tejido Nervioso , Reacción en Cadena en Tiempo Real de la Polimerasa , Semaforina-3A/metabolismoRESUMEN
Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D) is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERß) participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERß on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERß was observed in SKOV-3 cells. Forced over-expression of ERα and ERß in SKOV-3 cells was manipulated to establish ERα+ and ERß+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17ß-estradiol (E2) significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERß+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERß activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERß+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERß negatively regulated sema 4D expression and inhibited cell multiplication.
Asunto(s)
Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Neoplasias Ováricas/metabolismo , Semaforinas/metabolismo , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Regulación hacia Abajo , Femenino , Humanos , Semaforinas/genéticaRESUMEN
Ovarian cancer is one of the most common malignancies in women. Semaphorin 4D (sema 4D) is involved in the progress of multiple cancers. In the presence of estrogen-like ligands, estrogen receptors (ERα and ERβ) participate in the progress of breast and ovarian cancers by transcriptional regulation. The aim of the study was to investigate the role of sema 4D and elucidate the regulatory pattern of ERα and ERβ on sema 4D expression in ovarian cancers. Sema 4D levels were up-regulated in ovarian cancer SKOV-3 cells. Patients with malignant ovarian cancers had significantly higher sema 4D levels than controls, suggesting an oncogene role of sema 4D in ovarian cancer. ERα expressions were up-regulated in SKOV-3 cells compared with normal ovarian IOSE80 epithelial cells. Conversely, down-regulation of ERβ was observed in SKOV-3 cells. Forced over-expression of ERα and ERβ in SKOV-3 cells was manipulated to establish ERα+ and ERβ+ SKOV-3 cell lines. Incubation of ERα+ SKOV-3 cells with ERs agonist 17β-estradiol (E2) significantly enhanced sema 4D expression and rate of cell proliferation. Incubated with E2, ERβ+ SKOV-3 cells showed lower sema 4D expression and cell proliferation. Blocking ERα and ERβ activities with ICI182-780 inhibitor, sema 4D expressions and cell proliferation of ERα+ and ERβ+ SKOV-3 cells were recovered to control levels. Taken together, the data showed that sema 4D expression was positively correlated with the progress of ovarian cancer. ERα positively regulated sema 4D expression and accelerated cell proliferation. ERβ negatively regulated sema 4D expression and inhibited cell multiplication.
Asunto(s)
Humanos , Femenino , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Neoplasias Ováricas/metabolismo , Semaforinas/metabolismo , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Regulación hacia Abajo , Semaforinas/genéticaRESUMEN
The aim of the current study was to explore mechanisms of SEMA3B gene expression and its clinical significance in glioma, and provide a theoretical foundation for investigating individualized treatment in glioma. Paraffin-embedded tissues from 43 patients with a confirmed clinical diagnosis of glioma following neurosurgery at the First Affiliated Hospital of Zhengzhou University from December 2013 to April 2014 were selected randomly. An additional three normal brain tissues were obtained following encephalic decompression excision due to acute craniocerebral injury in the same period, which were used as the control group. Immunohistochemical staining for vascular endothelial growth factor was performed on the glioma tissues from the 43 patients. Genomic DNA was extracted for bisulfate conversion and sequencing. SEMA3B was fully expressed in the three normal brain tissues, and incompletely expressed in the 43 glioma tissues, with a lack of expression in 48.8% (21/43) of samples. Moreover, 58% of high-grade gliomas (grade III and IV) lacked SEMA3B expression, which was significantly more than those that lacked expression (20%) in low-grade gliomas (grade I and II), indicating that, as the clinical pathological grade increased, SEMA3B expression decreased. The occurrence and development of malignant tumors is a product of multiple genes and other factors. Here, we provide theoretical basis for glioma development and prognosis involving DNA-methylation driven silencing of SEMA3B, and thus, SEMA3B is a potential target for directed treatments against glioma.
Asunto(s)
Biomarcadores de Tumor/genética , Neoplasias Encefálicas/metabolismo , Silenciador del Gen , Glioma/metabolismo , Glicoproteínas de Membrana/genética , Semaforinas/genética , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Estudios de Casos y Controles , Metilación de ADN , Femenino , Glioma/genética , Glioma/patología , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Persona de Mediana Edad , Semaforinas/metabolismoRESUMEN
Human lymphotropic virus type 1 (HTLV-1) is a retrovirus causing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a neurodegenerative central nervous system (CNS) axonopathy. This virus mainly infects CD4(+) T lymphocytes without evidence of neuronal infection. Viral Tax, secreted from infected lymphocytes infiltrated in the CNS, is proposed to alter intracellular pathways related to axonal cytoskeleton dynamics, producing neurological damage. Previous reports showed a higher proteolytic release of soluble Semaphorin 4D (sSEMA-4D) from CD4(+) T cells infected with HTLV-1. Soluble SEMA-4D binds to its receptor Plexin-B1, activating axonal growth collapse pathways in the CNS. In the current study, an increase was found in both SEMA-4D in CD4(+) T cells and sSEMA-4D released to the culture medium of peripheral blood mononuclear cells (PBMCs) from HAM/TSP patients compared to asymptomatic carriers and healthy donors. After a 16-h culture, infected PBMCs showed significantly higher levels of CRMP-2 phosphorylated at Ser(522). The effect was blocked either with anti-Tax or anti-SEMA-4D antibodies. The interaction of Tax and sSEMA-4D was found in secreted medium of PBMCs in patients, which might be associated with a leading role of Tax with the SEMA-4D-Plexin-B1 signaling pathway. In infected PBMCs, the migratory response after transwell assay showed that sSEMA-4D responding cells were CD4(+)Tax(+) T cells with a high CRMP-2 pSer(522) content. In the present study, the participation of Tax-sSEMA-4D in the reduction in neurite growth in PC12 cells produced by MT2 (HTLV-1-infected cell line) culture medium was observed. These results lead to the participation of plexins in the reported effects of infected lymphocytes on neuronal cells.
Asunto(s)
Antígenos CD/genética , Productos del Gen tax/genética , Virus Linfotrópico T Tipo 1 Humano/metabolismo , Leucocitos Mononucleares/metabolismo , Neuritas/efectos de los fármacos , Paraparesia Espástica Tropical/metabolismo , Semaforinas/genética , Animales , Anticuerpos Neutralizantes/farmacología , Antígenos CD/metabolismo , Portador Sano , Estudios de Casos y Controles , Movimiento Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Regulación de la Expresión Génica , Productos del Gen tax/metabolismo , Virus Linfotrópico T Tipo 1 Humano/genética , Humanos , Células K562 , Leucocitos Mononucleares/patología , Leucocitos Mononucleares/virología , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Neuritas/metabolismo , Neuritas/ultraestructura , Células PC12 , Paraparesia Espástica Tropical/genética , Paraparesia Espástica Tropical/patología , Paraparesia Espástica Tropical/virología , Cultivo Primario de Células , Ratas , Receptores de Superficie Celular/genética , Receptores de Superficie Celular/metabolismo , Semaforinas/metabolismo , Transducción de SeñalRESUMEN
Leukocyte migration is essential for the function of the immune system. Their recruitment from the vessels to the tissues involves sequential molecular interactions between leukocytes and endothelial cells (ECs). Many adhesion molecules involved in this process have already been described. However, additional molecules may be important in this interaction, and here we explore the potential role for CD100 and plexins in monocyte-EC binding. CD100 was shown to be involved in platelet-endothelial cell interaction, an important step in atherogenesis and thrombus formation. In a recent work we have described CD100 expression in monocytes and in macrophages and foam cells of human atherosclerotic plaques. In the present work, we have identified plexin B2 as a putative CD100 receptor in these cells. We have detected CD100 expression in the endothelium as well as in in vitro cultured endothelial cells. Blocking of CD100, plexin B1 and/or B2 in adhesion experiments have shown that both CD100 and plexins act as adhesion molecules involved in monocyte-endothelial cell binding. This effect may be mediated by CD100 expressed in both cell types, probably coupled to the receptors endothelial plexin B1 and monocytic plexin B2. These results can bring new insights about a possible biological activity of CD100 in monocyte adhesion and atherosclerosis, as well as a future candidate for targeting therapeutics.
Asunto(s)
Antígenos CD/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/patología , Moléculas de Adhesión Celular/metabolismo , Células Endoteliales de la Vena Umbilical Humana/citología , Monocitos/citología , Proteínas del Tejido Nervioso/metabolismo , Receptores de Superficie Celular/metabolismo , Semaforinas/metabolismo , Animales , Antígenos CD/genética , Arterias Carótidas/metabolismo , Arterias Carótidas/patología , Adhesión Celular , Diferenciación Celular , Células Cultivadas , Células Espumosas/metabolismo , Regulación de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Ratones , ARN Mensajero/genética , ARN Mensajero/metabolismo , Semaforinas/genéticaRESUMEN
BACKGROUND: Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H2O2. The expression of HKII in MSCs exposed to H2O2 was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H2O2 on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H2O2-induced apoptosis of MSC was evaluated. RESULTS: H2O2 (600 µM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H2O2 increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H2O2-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H2O2. CONCLUSIONS: These findings suggest that H2O2-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues.
Asunto(s)
Apoptosis , Glioma/patología , Hexoquinasa/metabolismo , Peróxido de Hidrógeno/toxicidad , Células Madre Mesenquimatosas/patología , MicroARNs/metabolismo , Diferenciación Celular , Movimiento Celular , Supervivencia Celular , Glioma/metabolismo , Humanos , Peróxido de Hidrógeno/administración & dosificación , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/enzimología , MicroARNs/antagonistas & inhibidores , Mitocondrias/enzimología , Invasividad Neoplásica , Especies Reactivas de Oxígeno , Reacción en Cadena en Tiempo Real de la Polimerasa , Semaforinas/genética , Semaforinas/metabolismoRESUMEN
KLK7 substrate specificity was evaluated by families of fluorescence resonance energy transfer (FRET) peptides derived from Abz-KLFSSK-Q-EDDnp (Abz=ortho-aminobenzoic acid and Q-EDDnp=glutaminyl-N-[2,4-dinitrophenyl] ethylenediamine), by one bead-one peptide FRET peptide library in PEGA resin, and by the FRET peptide libraries Abz-GXX-Z-XX-Q-EDDnp (Z and X are fixed and random natural amino acids, respectively). KLK7 hydrolyzed preferentially F, Y or M, and its S1' and S2' subsites showed selectivity for hydrophilic amino acids, particularly R and K. This set of specificities was confirmed by the efficient kininogenase activity of KLK7 on Abz-MISLM(↓)KRPPGFSPF(↓)RSSRI-NH2 ((↓)indicates cleavage), hydrolysis of somatostatin and substance P and inhibition by kallistatin. The peptide Abz-NLY(↓)RVE-Q-EDDnp is the best synthetic substrate so far described for KLK7 [kcat/Km=455 (mMs)(-1)] that was designed from the KLK7 substrate specificity analysis. It is noteworthy that the NLYRVE sequence is present in human semaphorin 6B. KLK7 is activated by GAGs, inhibited by neutral salts, and activated by high concentration of kosmotropic salt. Pyroglutamic acid inhibited KLK7 (Ki=33mM) and is present in skin moisturizing factor (124mM). The KLK7 specificity described here and elsewhere reflects its participation in patho-physiological events in skin, the gastrointestinal tract and central nervous system, where KLK7 is significantly expressed.
Asunto(s)
Glicosaminoglicanos/farmacología , Calicreínas/metabolismo , Péptido Hidrolasas/metabolismo , Péptidos/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Biocatálisis/efectos de los fármacos , Transferencia Resonante de Energía de Fluorescencia , Humanos , Hidrólisis/efectos de los fármacos , Cinética , Quininógenos/metabolismo , Datos de Secuencia Molecular , Concentración Osmolar , Ácido Pirrolidona Carboxílico/farmacología , Semaforinas/metabolismo , Serpinas/metabolismo , Somatostatina/metabolismo , Sustancia P/metabolismo , Especificidad por Sustrato , Factores de TiempoRESUMEN
BACKGROUND: Low survival rate of transplanted cells compromises the efficacy of cell therapy. Hexokinase II (HKII) is known to have anti-apoptotic activity through its interaction with mitochondria. The objective was to identify miRNAs targeting HKII and investigate whether miRNA-mediated modulation of HKII could improve the survival of mesenchymal stem cells (MSCs) exposed to H2O2. The expression of HKII in MSCs exposed to H2O2 was evaluated, and HKII-targeting miRNA was screened based on miRNA-target prediction databases. The effect of H2O2 on the expression of the selected HKII-targeting miRNA was examined and the effect of modulation of the selected HKII-targeting miRNA using anti-miRNA on H2O2-induced apoptosis of MSC was evaluated. RESULTS: H2O2 (600 µM) induced cell death of MSCs and decreased mitochondrial HKII expression. We have identified miR-181a as a HKII-targeting miRNA and H2O2 increased the expression of miR-181a in MSCs. Delivery of anti-miR-181a, which neutralizes endogenous miR-181a, significantly attenuated H2O2-induced decrease of HKII expression and disruption of mitochondrial membrane potential, improving the survival of MSCs exposed to H2O2. CONCLUSIONS: These findings suggest that H2O2-induced up-regulation of miR-181a contributes to the cell death of MSCs by down-regulating HKII. Neutralizing miR-181a can be an effective way to prime MSCs for transplantation into ischemic tissues.
Asunto(s)
Humanos , Apoptosis , MicroARNs/metabolismo , Células Madre Mesenquimatosas/patología , Glioma/patología , Hexoquinasa/metabolismo , Peróxido de Hidrógeno/toxicidad , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Diferenciación Celular , Movimiento Celular , Supervivencia Celular , Especies Reactivas de Oxígeno , Semaforinas/genética , Semaforinas/metabolismo , MicroARNs/antagonistas & inhibidores , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/enzimología , Reacción en Cadena en Tiempo Real de la Polimerasa , Glioma/metabolismo , Peróxido de Hidrógeno/administración & dosificación , Mitocondrias/enzimología , Invasividad NeoplásicaRESUMEN
Atherosclerosis is a complex disease in which vessels develop plaques comprising dysfunctional endothelium, monocyte derived lipid laden foam cells and activated lymphocytes. Considering that humans and animal models of the disease develop quite distinct plaques, we used human plaques to search for proteins that could be used as markers of human atheromas. Phage display peptide libraries were probed to fresh human carotid plaques, and a bound phage homologous to plexin B1, a high affinity receptor for CD100, was identified. CD100 is a member of the semaphorin family expressed by most hematopoietic cells and particularly by activated T cells. CD100 expression was analyzed in human plaques and normal samples. CD100 mRNA and protein were analyzed in cultured monocytes, macrophages and foam cells. The effects of CD100 in oxLDL-induced foam cell formation and in CD36 mRNA abundance were evaluated. Human atherosclerotic plaques showed strong labeling of CD100/SEMA4D. CD100 expression was further demonstrated in peripheral blood monocytes and in in vitro differentiated macrophages and foam cells, with diminished CD100 transcript along the differentiation of these cells. Incubation of macrophages with CD100 led to a reduction in oxLDL-induced foam cell formation probably through a decrease of CD36 expression, suggesting for the first time an atheroprotective role for CD100 in the human disease. Given its differential expression in the numerous foam cells and macrophages of the plaques and its capacity to decrease oxLDL engulfment by macrophages we propose that CD100 may have a role in atherosclerotic plaque development, and may possibly be employed in targeted treatments of these atheromas.
Asunto(s)
Antígenos CD/metabolismo , Biomarcadores/metabolismo , Células Espumosas/metabolismo , Macrófagos/metabolismo , Placa Aterosclerótica/química , Semaforinas/metabolismo , Análisis de Varianza , Western Blotting , Antígenos CD36/metabolismo , Técnicas de Visualización de Superficie Celular , Células Cultivadas , Cartilla de ADN/genética , Técnica del Anticuerpo Fluorescente , Humanos , Inmunohistoquímica , Proteínas del Tejido Nervioso/metabolismo , Placa Aterosclerótica/metabolismo , ARN Mensajero/metabolismo , Receptores de Superficie Celular/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Cell migration is a crucial event for normal T-cell development, and various ligand/receptor pairs have been implicated. Most of them, including chemokines and extracellular matrix proteins, have attractant properties on thymocytes. We discuss herein two further groups of ligand/receptor pairs, semaphorins/neuropilins and ephs/ephrins, which are constitutively expressed by thymocytes and thymic microenvironmental cells. Evidence shows that the corresponding interactions are relevant for developing T-cell migration, including the entry of bone marrow progenitor cells, migration of CD4/CD8-defined thymocyte subpopulations triggered by chemokines and/or extracellular matrix proteins, and thymocyte export. Conceptually, the data summarized here show that thymocyte migration results from a complex network of molecular interactions, which generate not only attraction, but also repulsion of migrating T-cell precursors.
Asunto(s)
Movimiento Celular/fisiología , Efrinas/metabolismo , Semaforinas/metabolismo , Timocitos/fisiología , Animales , Efrinas/genética , Regulación de la Expresión Génica , Semaforinas/genéticaRESUMEN
Some molecules described in the nervous system are also expressed in cells involved in the control of the immune response, suggesting they have a role as common mechanisms between neuroendocrine and immune systems. In this review, we focus on the expression and role of neuropilins (NPs) and their soluble ligands class 3 semaphorins in thymus physiology, particularly migration of developing thymocytes. We also discuss the concept of multivectorial thymocyte migration, including semaphorins, as a new individual cell migration vector.
Asunto(s)
Neuropilinas/metabolismo , Semaforinas/metabolismo , Timo/citología , Timo/metabolismo , Animales , Movimiento Celular , Humanos , Sistema Nervioso/metabolismo , Linfocitos T/citología , Linfocitos T/metabolismo , Timo/patologíaRESUMEN
Dynamic responses of uterine sympathetic nerves to changes in the circulating levels of sex hormones represent one of the most remarkable examples of physiological plasticity in the adult autonomic nervous system. The density of uterine sympathetic nerves is markedly and irreversibly reduced following puberty, and shows phases of degeneration and regeneration during the natural oestrous cycle. Even more remarkable, uterine sympathetic nerves degenerate during normal pregnancy and regenerate following delivery. Plasticity in uterine sympathetic nerves was initially interpreted as a selective effect of sex hormones on the system of paracervical short adrenergic neurons supplying the uterus. In the last decade, the alternative explanation that sex hormones might alter the ability of the uterine tissue to support its innervation began to be explored and current evidence indicates that oestrogen and pregnancy elicit changes in the neuritogenic properties of the target uterine tissue. In addition, there are indications that sex hormones may also affect the receptivity of uterine-related sympathetic neurons to target-derived signals. Although the nature of these signals is still fragmentary, there is evidence for the contribution of a range of molecules, including neurotrophins, pro-neurotrophins and chemorepulsive signals of the semaphorin family. This review summarizes some general features of plasticity in uterine sympathetic nerves and highlights recent investigations of the cellular and molecular mechanisms underlying this dramatic model of natural plasticity.
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Ciclo Estral/fisiología , Hormonas Esteroides Gonadales/metabolismo , Plasticidad Neuronal/fisiología , Sistema Nervioso Simpático/metabolismo , Útero/inervación , Útero/fisiología , Animales , Femenino , Humanos , Inflamación/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Regeneración Nerviosa/fisiología , Embarazo , Semaforinas/metabolismo , Sistema Nervioso Simpático/citologíaRESUMEN
Endometrial stromal sarcoma is a rare neoplasm of the uterus. Extrauterine locations of this neoplasm, excluding metastases or local extension, are even more unusual and are usually associated with the presence of endometriosis. The authors report a case of endometrial stromal sarcoma presenting as a vaginal wall nodule, without any sign of primary uterine tumor after extensive evaluation or presence of endometriosis. The morphology, immunohistochemical profile, differential diagnoses, and pathogenesis are discussed, as well as a review of the literature on this issue.