RESUMEN
A macroscopic effect can be induced by a local non-Hermitian term in a many-body system, when it manifests simultaneously level coalescence of a full real degeneracy spectrum, leading to exceptional spectrum. In this paper, we propose a family of systems that support such an intriguing property. It is generally consisted of two arbitrary identical Hermitian sub-lattices in association with unidirectional couplings between them. We show exactly that all single-particle eigenstates coalesce in pairs even only single unidirectional coupling appears. It means that all possible initial states obey the exceptional dynamics, resulting in some macroscopic phenomena, which never appears in a Hermitian system. As an application, we study the dynamic magnetization induced by complex fields in an itinerant electron system. It shows that an initial saturated ferromagnetic state at half-filling can be driven into its opposite state according to the dynamics of high-order exceptional point. Any Hermitian quench term cannot realize a steady opposite saturated ferromagnetic state. Numerical simulations for the dynamical processes of magnetization are performed for several representative situations, including lattice dimensions, global random and local impurity distributions. It shows that the dynamic magnetization processes exhibit universal behavior.
RESUMEN
Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA HOXA-AS2 acts as an oncogene by targeting miR-145-3p in human non-small cell lung cancer, by Y.-B. Shi, S.-L. Liu, X.-R. Mou, J. Liao, J.-P. Che, X.-Q. Fei, A.-R. Wang, published in Eur Rev Med Pharmacol Sci 2020; 24 (3): 1243-1249-DOI: 10.26355/eurrev_202002_20177-PMID: 32096154" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20177.
RESUMEN
OBJECTIVE: Recent studies have proved that long non-coding RNAs (lncRNAs) play important roles in many diseases, especially malignancies. The aim of this study was to investigate the exact role of lncRNA HOXA-AS2 (Hoxa cluster antisense RNA 2) in the development of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to detect HOXA-AS2 expression in NSCLC patients. The Wound healing assay and transwell assay were conducted to explore the function of HOXA-AS2 on NSCLC metastasis. Furthermore, the mechanism assays were used to explore the interaction between HOXA-AS2 and microRNA-145-3p (miR-145-3p). RESULTS: HOXA-AS2 expression level in NSCLC tissues was significantly higher than adjacent tissues. HOXA-AS2 expression was negatively correlated with disease-free survival of NSCLC patients. Moreover, the functional assays showed that the migration and invasion of NSCLC cells were significantly inhibited after HOXA-AS2 in vitro silence. Furthermore, the luciferase reporter gene assay also revealed that miR-145-3p was a direct target of HOXA-AS2 in NSCLC. CONCLUSIONS: Our results indicated that HOXA-AS2 could enhance the migration and invasion abilities of NSCLC by targeting miR-145-3p. Furthermore, these findings suggested that HOXA-AS2 might be a potential therapeutic target for NSCLC.
RESUMEN
In the non-destructive testing of ferromagnetic pipes based on remote field eddy currents, an array of sensing coils is often used to detect local defects. While testing, the image that is obtained by sensing coils exhibits a ghost-image, which originates from both the transmitter and sensing coils passing over the same defects in pipes. Ghost-images are caused by transmitters and lead to undesirable assessments of defects. In order to remove ghost-images, two pickup coils are coaxially set to each other in remote field. Due to the time delay between differential signals tested by the two pickup coils, a Wiener deconvolution filter is used to identify the artificial peaks that lead to ghost-images. Because the sensing coils and two pickup coils all receive the same signal from one transmitter, they all contain the same artificial peaks. By subtracting the artificial peak values obtained by the two pickup coils from the imaging data, the ghost-image caused by the transmitter is eliminated. Finally, a relatively highly accurate image of local defects is obtained by these sensing coils. With proposed method, there is no need to subtract the average value of the sensing coils, and it is sensitive to ringed defects.
RESUMEN
We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Fístula Arteriovenosa/complicaciones , Hipertensión Pulmonar/etiología , Diálisis Peritoneal/efectos adversos , Proteína C-Reactiva/análisis , China/epidemiología , Hipertensión Pulmonar/epidemiología , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Péptido Natriurético Encefálico/sangre , Fósforo/sangre , Estudios Prospectivos , Factores de RiesgoRESUMEN
We investigated the risk factors for pulmonary hypertension (PH) in patients receiving maintenance peritoneal dialysis (MPD). A group of 180 end-stage renal disease patients (124 men and 56 women; mean age: 56.43±8.36) were enrolled in our study, which was conducted between January 2009 and June 2014. All of the patients received MPD treatment in the Dialysis Center of the Second Affiliated Hospital of Soochow University. Clinical data, laboratory indices, and echocardiographic data from these patients were collected, and follow-ups were scheduled bi-monthly. The incidence and relevant risk factors of PH were analyzed. The differences in measurement data were compared by t-test and enumeration data were compared with the χ2 test. Among the 180 patients receiving MPD, 60 were diagnosed with PH. The remaining 120 were regarded as the non-PH group. Significant differences were observed in the clinical data, laboratory indices, and echocardiographic data between the PH and non-PH patients (all P<0.05). Furthermore, hypertensive nephropathy patients on MPD showed a significantly higher incidence of PH compared with non-hypertensive nephropathy patients (P<0.05). Logistic regression analysis showed that the proportion of internal arteriovenous fistula, C-reactive protein levels, and ejection fraction were the highest risk factors for PH in patients receiving MPD. Our study shows that there is a high incidence of PH in patients receiving MPD and hypertensive nephropathy patients have an increased susceptibility to PH.
Asunto(s)
Fístula Arteriovenosa/complicaciones , Hipertensión Pulmonar/etiología , Diálisis Peritoneal/efectos adversos , Anciano , Proteína C-Reactiva/análisis , China/epidemiología , Femenino , Humanos , Hipertensión Pulmonar/epidemiología , Incidencia , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fósforo/sangre , Estudios Prospectivos , Factores de RiesgoRESUMEN
OBJECTIVE: To assess the examination methods, the multidetector CT (MDCT), and findings of bowel and mesenteric injuries in blunt trauma and the evaluation for clinical management. PATIENTS AND METHODS: Retrospectively analysis examination methods, image reformation, the sensitivity and specificity of variant appearance in MDCT of 43 cases of bowel and mesenteric injuries which were conformed by operation. RESULTS: Contrast enhancement thin CT with multi-plannar reconstruction MPR can improve the sensitivity of bowel and mesenteric injuries. Appearance of bowel and mesenteric injuries in MDCT included below: patchy or focal bowel wall thickening in 67.4%, intraperitoneal free air in 25.6%, mesenteric infiltration in 90.7%, and intraperitoneal fluid in 81.4%. Bowel wall discontinuity and intraperitoneal free air are specific to bowel injuries, whereas asymmetric bowel wall thickening, irregular enhancement of bowel wall, blurred serous membrane, and fluid of intestinal loop are strongly suggestive to bowel and mesenteric injuries. CONCLUSIONS: Contrast enhancement thin CT with MPR can help improve to show direct and indirect sigh of bowel and mesenteric injuries with higher sensitivity and specificity.
Asunto(s)
Traumatismos Abdominales/diagnóstico , Intestinos/lesiones , Mesenterio/lesiones , Tomografía Computarizada por Rayos X , Heridas no Penetrantes/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Several previous studies have demonstrated that elevated levels of fibroblast growth factor-23 (FGF-23) may be involved in atherosclerosis and contribute to the high mortality rate of peritoneal dialysis (PD) patients. The aim of this study was to determine the precise role of FGF-23 in the pathogenesis of atherosclerosis in PD patients. Between April 2009 and January 2012, 62 PD patients and 25 control subjects were included in the study. An enzyme-linked immunosorbent assay was conducted to test for plasma FGF-23 levels. Carotid artery intima-media thickness (CIMT), left ventricular mass index (LVMI), and myocardial performance index (MPI) were determined by ultrasonography. Plasma Ca(2+), P(3+), calcium-phosphorus product, parathyroid hormone, N-terminal pro-brain natriuretic peptide, and cardiac troponin I were also detected. Plasma FGF-23 levels in PD patients were significantly higher than those in control subjects. PD patients with CIMT > 1.0 mm showed the highest levels of FGF-23. Plasma P(3+), calcium-phosphorous product, plasma parathyroid hormone, CIMT, LVMI, and MPI levels were positively associated with plasma FGF-23 levels. Multiple-stepwise regression analyses revealed that plasma P(3+), plasma parathyroid hormone, CIMT, LVMI, and MPI levels were strongly associated with plasma FGF-23 levels. However, no correlations were observed in plasma N-terminal pro-brain natriuretic hormone and cardiac troponin I levels. Plasma FGF- 23 levels may play an important role in the initiation and progression of atherosclerosis. Thus, detecting and defining plasma FGF-23 levels may be a promising biomarker for the early detection of atherosclerosis in PD patients.
Asunto(s)
Aterosclerosis/genética , Biomarcadores/sangre , Factores de Crecimiento de Fibroblastos/sangre , Diálisis Peritoneal , Adulto , Anciano , Aterosclerosis/sangre , Aterosclerosis/patología , Femenino , Factor-23 de Crecimiento de Fibroblastos , Humanos , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Hormona Paratiroidea/sangre , Factores de Riesgo , Troponina I/sangreRESUMEN
A new ultrahigh-energy-resolution and wide-energy-range soft X-ray beamline has been designed and is under construction at the Shanghai Synchrotron Radiation Facility. The beamline has two branches: one dedicated to angle-resolved photoemission spectroscopy (ARPES) and the other to photoelectron emission microscopy (PEEM). The two branches share the same plane-grating monochromator, which is equipped with four variable-line-spacing gratings and covers the 20-2000â eV energy range. Two elliptically polarized undulators are employed to provide photons with variable polarization, linear in every inclination and circular. The expected energy resolution is approximately 10â meV at 1000â eV with a flux of more than 3 × 10(10)â photonsâ s(-1) at the ARPES sample positions. The refocusing of both branches is based on Kirkpatrick-Baez pairs. The expected spot sizes when using a 10â µm exit slit are 15â µm × 5â µm (horizontal × vertical FWHM) at the ARPES station and 10â µm × 5â µm (horizontal × vertical FWHM) at the PEEM station. The use of plane optical elements upstream of the exit slit, a variable-line-spacing grating and a pre-mirror in the monochromator that allows the influence of the thermal deformation to be eliminated are essential for achieving the ultrahigh-energy resolution.
RESUMEN
OBJECTIVE: Aristolochic acid nephropathy (AAN) is a progressive renal interstitial fibrosis disease that was initially reported among a Belgian cohort of about 50 patients after the intake of diet pills containing the Chinese herb Aristolochia fangchi. In addition to renal disease, foci of AAN show increased incidences of urothelial carcinomas (UC). Immunosuppression is associated with an increased risk for the development of different malignancies. Our aim was to examine the outcomes of UC among patients with AAN after transplantation in China, the cradle of this traditional medicine. PATIENTS AND METHODS: We performed a retrospective evaluation of the charts and pathology reports of 1612 renal transplant recipients treated at our 2 institutions. RESULTS: From January 1998 to December 2006, we performed cadaveric kidney transplantations in 17 patients with AAN, all of whom were treated with cyclosporine plus azathioprine or mycophenolate mofetil plus prednisone. One-year graft survival was 100%. During the mean follow-up of 57 months (range, 21-108 months), 9 recipients (52.9%) developed UC, compared with a 0.46% prevalence of urinary tract tumors among other Chinese kidney transplant recipients. The age at which the diagnosis was made ranged from 39 to 66 years (mean, 53.6 +/- 6.8 years). Among the 9 patients with UC, 8 cases (88.9%) involved the upper urinary tract: bilateral, 3 cases, 37.5%; unilateral, 5 cases, 62.5%. In 1 patient only a bladder tumor was detected. Two patients showed the bladder, synchronous bilateral ureter, and pelvis to be involved. All patients with UC underwent surgical treatment, recovering uneventfully with functioning grafts after tumor excision, except 1 patient who underwent nephrectomy of the transplanted kidney. Six patients (75%) experienced recurrences during the follow-up period. Three patients died within a mean of 20 months (range, 1-42 months) after tumor excision. CONCLUSIONS: The risk for UC is increased among patients with AAN after transplantation. Regular screening for early detection of malignancy is mandatory. Longer follow-up and results from other transplant centers are needed to further investigate the relationship between AAN and UC among renal transplant patients.
Asunto(s)
Antivirales/toxicidad , Ácidos Aristolóquicos/toxicidad , Carcinoma de Células Transicionales/cirugía , Trasplante de Riñón/efectos adversos , Riñón/patología , Neoplasias Urológicas/cirugía , Adulto , Anciano , Cadáver , Carcinoma de Células Transicionales/inducido químicamente , China , Femenino , Humanos , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Donantes de Tejidos , Neoplasias Urológicas/inducido químicamenteRESUMEN
OBJECTIVES: To investigate potential effects of ebselen and ethylhydroxyethyl cellulose (EHEC) on the acute phase responses and the severity of multiple organ dysfunction associated with acute pancreatitis. METHODS: Acute pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate. The increase of total protein content in the BALF was used as an indication for acute lung injury, plasma amylase for pancreatic damage, plasma bilirubin for acute liver dysfunction, and plasma creatinine for acute kidney dysfunction. Levels of interleukin (IL)-6, macrophage inflammatory protein (MIP)-2 in the BALF were determined by ELISA. RESULTS: There was a dose-related tendency for ebselen or EHEC alone to prevent organ dysfunction and reduce elevated plasma levels of IL-6 and ICAM-1 expression on circulating leukocytes 12 h after AP induction. The combination of ebselen and EHEC significantly prevented pancreatitis-induced multiple organ injury, IL-6 production and ICAM-1 expression in rats and exhibited better effects than either monocompound alone. CONCLUSION: The combination of ebselen and EHEC may be a new potential for treatment of acute severe pancreatitis.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Azoles/farmacología , Celulosa/análogos & derivados , Factores Inmunológicos/farmacología , Insuficiencia Multiorgánica/prevención & control , Compuestos de Organoselenio/farmacología , Pancreatitis/tratamiento farmacológico , Amilasas/sangre , Animales , Bilirrubina/sangre , Líquido del Lavado Bronquioalveolar/química , Celulosa/farmacología , Quimiocina CXCL2 , Quimiocinas CXC/inmunología , Creatina/sangre , Nutrición Enteral , Molécula 1 de Adhesión Intercelular/inmunología , Interleucina-6/sangre , Isoindoles , Masculino , Monocitos/inmunología , Insuficiencia Multiorgánica/sangre , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/inmunología , Pancreatitis/sangre , Pancreatitis/inducido químicamente , Pancreatitis/inmunología , Proteínas/análisis , Ratas , Ratas Sprague-Dawley , Ácido TaurodesoxicólicoRESUMEN
The extracellular matrix (ECM) serves as a medium for cell-cell interactions and can directly signal cells through cell surface ECM receptors, such as integrins. In addition, many growth factors and signaling molecules are stored in the ECM. Thus, ECM remodeling and/or degradation plays a critical role in cell fate and behavior during many developmental and pathological processes. ECM remodeling/degradation is, to a large extent, mediated by matrix metalloproteinases (MMPs), a family of extracellular or membrane-bound, Zn2+-dependent proteases that are capable of digesting various proteinaceous components of the ECM. Of particular interest among them is the MMP11 or stromelysin-3, which was first isolated as a breast cancer associated protease. Here, we review some evidence for the involvement of this MMP in development and diseases with a special emphasis on amphibian metamorphosis, a postembryonic, thyroid hormone-dependent process that transforms essentially every organ/tissue of the animal.
Asunto(s)
Embrión no Mamífero/enzimología , Metaloendopeptidasas/metabolismo , Invasividad Neoplásica/patología , Metástasis de la Neoplasia/patología , Animales , Metaloproteinasa 11 de la Matriz , XenopusAsunto(s)
Cromosomas Humanos Y/genética , Pérdida Auditiva/genética , Audiometría/métodos , China , Cromosomas Humanos Par 9/genética , Salud de la Familia , Femenino , Ligamiento Genético , Pérdida Auditiva/patología , Humanos , Escala de Lod , Modelos Logísticos , Masculino , Repeticiones de Microsatélite , Análisis Multivariante , Linaje , Penetrancia , FenotipoRESUMEN
Many nuclear hormone receptors (NHRs) actively repress the expression of their primary response genes through the recruitment of transcriptional corepressor complexes to regulated promoters. N-CoR and the highly related SMRT were originally isolated and characterized by their ability to interact exclusivelywith the unliganded forms of NHRs and confer transcriptional repression. Recently, both the N-CoR and SMRT corepressors have been found to exist in vivo in multiple, distinct macromolecular complexes. While these corepressor complexes differ in overall composition, a general theme is that they contain histone deacetylase enzymatic activity. Several of these complexes contain additional transcriptional corepressor proteins with functional ties to chromatin structure. Together, these data suggest that modulation of chromatin structure plays a central role in N-CoR mediated transcriptional repression from unliganded NHRs.
Asunto(s)
Cromatina/metabolismo , Regulación de la Expresión Génica , Histona Desacetilasas/metabolismo , Proteínas Nucleares/metabolismo , Receptores Citoplasmáticos y Nucleares/metabolismo , Proteínas Represoras/metabolismo , Transcripción Genética , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Células HeLa , Histona Desacetilasas/genética , Humanos , Proteínas Nucleares/genética , Co-Represor 1 de Receptor Nuclear , Co-Represor 2 de Receptor Nuclear , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Represoras/genética , Xenopus laevisRESUMEN
Thyroid hormone (TH) affects a wide variety of biological processes, from development to physiological function of different cells and organs. Alterations in plasma TH concentrations lead to developmental abnormalities and pathological consequences. Earlier studies have observed that plasma TH levels vary in AIDS patients such that low levels of TH correlate with survival rate. Furthermore, studies on the regulation of the human immunodeficiency virus type 1 (HIV-1) have shown that TH receptor (TR) is capable of binding to two regions within the long terminal repeat (LTR), which controls the transcription of HIV-1 genome. The frog oocyte is an in vivo system that allows microinjected DNA to be chromatinized in a process mimicking the process that occurs in somatic cells. Studies in the frog oocyte have provided in vivo evidence on the role of chromatin remodeling in transcriptional regulation by TR and have shown that TR utilizes similar mechanisms in the regulation of the HIV-1 LTR. That is, TR binds to LTR in chromatin in vivo and represses the LTR in the absence of TH by recruiting corepressor complexes containing histone deacetylases, and upon TH binding, TR causes chromatin remodeling and LTR activation.
Asunto(s)
Cromatina/metabolismo , Duplicado del Terminal Largo de VIH/fisiología , Histonas/metabolismo , Receptores de Hormona Tiroidea/fisiología , Acetilación , Secuencia de Bases , Regulación Viral de la Expresión Génica/fisiología , Humanos , Datos de Secuencia Molecular , Análisis de Secuencia de ADN , Transcripción Genética/fisiologíaRESUMEN
Thyroid hormones (THs) must be taken up by target cells to act at the genomic level through binding to nuclear thyroid hormone receptors (TRs). Extensive study has been made of mechanisms by which TH-bound TRs regulate transcription, yet little is known about the critical upstream step, i.e. how THs enter the cell. Growing evidence suggests that saturable transport mechanisms mediate the greater part of TH movement across the plasma membrane and have important roles in the regulation of TH bioavailability. For example, System L is a multifunctional transport system serving as a plasma membrane transporter of THs and amino acids in mammalian cells. We have used two complementary systems, the Xenopus oocyte (which has negligible basal System L activity) and the mammalian BeWo cell line (which has System L activity for TH transport), to investigate the role of this representative TH transporter in nuclear action of THs. We demonstrate that overexpression of System L in Xenopus oocytes increases both cytoplasmic and nuclear delivery of THs from external medium and also enhances transcriptional activation by TRs. Conversely, blocking endogenous System L activity in BeWo cells with specific inhibitors reduces both TH uptake and TR function. These results indicate that plasma membrane TH transporters such as System L may have important roles in gene regulation by TRs.
Asunto(s)
Proteínas Portadoras/metabolismo , Receptores de Hormona Tiroidea/genética , Hormonas Tiroideas/metabolismo , Transcripción Genética , Secuencia de Aminoácidos , Aminoácidos/metabolismo , Animales , Transporte Biológico , Núcleo Celular/genética , Núcleo Celular/metabolismo , Células Cultivadas , Coriocarcinoma/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Proteínas Inmediatas-Precoces/genética , Proteínas Inmediatas-Precoces/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Datos de Secuencia Molecular , Oocitos , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Receptores de Hormona Tiroidea/metabolismo , Receptores X Retinoide , Hormonas Tiroideas/farmacocinética , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Activación Transcripcional , Xenopus laevisRESUMEN
Amphibian metamorphosis is the result of thyroid hormone (TH)-induced organ transformations including de novo morphogenesis, tissue remodeling and resorption through programmed cell death (apoptosis). All changes during metamorphosis are presumed to be mediated through gene regulation cascades initiated by TH. Numerous studies have implicated important roles of chromatin remodeling in transcriptional regulation. In particular, several lines of evidence support the view that histone acetylation is associated with transcriptional activation and histone deacetylation leads to gene repression. Here we address the physiological roles of histone deacetylases during vertebrate postembryonic development by using amphibian metamorphosis as a model. We first demonstrate that Xenopus laevis Rpd3 (a histone deacetylase) and Sin3 (a corepressor associated to Rpd3) are expressed in premetamorphic and metamorphic tadpole tissues, suggesting their involvement in these postembryonic processes. To test this possibility, we use a histone deacetylase inhibitor, trichostatin A, to block histone deacetylases and examine the development of the tadpoles. Our results indicate both natural and T3-induced metamorphosis are blocked by the inhibitor. We further show that this drug inhibits metamorphosis in different tissues, whether they involve de novo development or resorption through apoptosis, and that it functions in a stage-dependent but organ-autonomous manner. The data thus support an important role of histone deacetylases in the gene regulation cascades induced by T3 during metamorphosis.
Asunto(s)
Desarrollo Embrionario , Histona Desacetilasas/fisiología , Proteínas de Saccharomyces cerevisiae , Xenopus laevis/crecimiento & desarrollo , Animales , Western Blotting , Embrión no Mamífero/enzimología , Inhibidores Enzimáticos/farmacología , Inhibidores de Histona Desacetilasas , Histona Desacetilasas/metabolismo , Ácidos Hidroxámicos/farmacología , Metamorfosis Biológica/efectos de los fármacos , Metamorfosis Biológica/fisiología , Morfogénesis , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Triyodotironina/farmacología , Proteínas de Xenopus/metabolismo , Xenopus laevis/embriologíaRESUMEN
Amphibian metamorphosis is marked by dramatic thyroid hormone (T(3))-induced changes including de novo morphogenesis, tissue remodeling and organ resorption through programmed cell death. These changes involve cascades of gene regulation initiated by thyroid hormone and its receptors. Previous studies suggest that chromatin remodeling involving changes in core histone acetylation plays a fundamental role in transcriptional regulation. A basic model has been suggested where targeted histone deacetylation is involved in transcriptional repression and histone acetylation is involved in transcriptional activation. On the other hand, the developmental roles of histone acetylation remain to be elucidated. Here we demonstrate that tadpole treatment with trichostatin A, a specific potent histone deacetylase inhibitor, blocks metamorphosis. Gene expression analyses show that trichostatin A induces the release of T(3)-response gene repression without affecting T(3)-induction of direct T(3)-response genes. However, the drug blocks the regulation of late T(3)-response genes, which may be responsible for its inhibitory effects on metamorphosis. These data support a role of deacetylases in transcriptional repression by unliganded T(3) receptor during premetamorphosis and another role at a downstream step of the gene regulation cascade induced by T(3) during metamorphosis.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica/fisiología , Histona Desacetilasas/metabolismo , Intestinos/crecimiento & desarrollo , Metamorfosis Biológica/fisiología , Animales , Apoptosis/fisiología , Cartilla de ADN , Activación Enzimática/fisiología , Inhibidores Enzimáticos/farmacología , Células Epiteliales/fisiología , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas , Ácidos Hidroxámicos/farmacología , Intestinos/citología , Metamorfosis Biológica/efectos de los fármacos , Receptores de Hormona Tiroidea/genética , Triyodotironina/farmacología , Triyodotironina/fisiología , Xenopus laevisRESUMEN
The extracellular matrix (ECM) functions as the structural support of cells and as a medium for cell-cell interactions. It is understood to play critical roles in development. ECM remodeling is mediated largely through the action of matrix metalloproteinases (MMPs), a family of Zn2+-dependent proteases capable of degrading various proteinaceous components of the ECM. MMPs are expressed in many developmental and pathologic processes. However, few studies have been carried out to investigate the function of MMPs during embryogenesis and postembryonic organogenesis. By using Xenopus development as a model system, we have previously shown that several MMP genes are expressed from neurulation to the completion of embryogenesis in distinct tissues/organs, suggesting that ECM remodeling during mid- to late embryogenesis occurs in an organ-specific manner. By using the recently developed transgenic technology for Xenopus laevis, we overexpressed Xenopus MMPs stromelysin-3 (ST3) and collagenase-4 (Col4) under the control of a ubiquitous promoter and observed that embryos with overexpressed ST3 or Col4, but not the control green fluorescent protein (GFP), died in a dose-dependent manner during late embryogenesis. The specificity of this embryonic lethal phenotype was confirmed by the failure of a catalytically inactive mutant of ST3 to affect development. Finally, overexpression of a mammalian membrane type-MMP also led to late embryonic lethality in Xenopus embryos, suggesting that membrane type-MMPs have functions in vivo for ECM remodeling, in addition to being activators of other pro-MMPs. These data together with the developmental expression of several MMPs during Xenopus development, suggest that MMPs play important roles during mid- to late embryogenesis and that proper regulation of MMP genes is critical for tissue morphogenesis and organogenesis.