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This study analyzes the mechanisms through which risk messages about climate change lead to people's risk information-sharing intention, and how digital media platform type serves as a context that moderates those mechanisms. Our analysis is informed by the influence of presumed influence (IPI) model, and we adapt and expand that model in three ways. First, we apply the concept of perceived media reach to the context of digital media platforms, specifically news aggregators and social networking sites. Second, we integrate the two mediators of risk perception and presumed influence. Third, we examine potential moderating roles of digital media platforms in the IPI model. An online survey was conducted among 1000 South Korean adults, and a moderated mediation model (PROCESS Macro Model 59) generated the following results. (1) Perceived media reach was positively related to both mediators-risk perception and presumed influence. (2) By way of those two mediators, perceived reach significantly led to information-sharing intention. (3) Presumed influence, but not risk perception, was significantly related to information-sharing intention. (4) Digital media platforms moderated the relation between perceived reach and risk perception: the role of content-related risk perception was more pronounced in news aggregators, while the role of context-related presumed influence was greater in social networking sites. Theoretical and practical implications for risk communication are discussed.
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Despite the rapidly increasing number of female gamers worldwide, female players are still experiencing discrimination, stereotyping, and objectification in digital games. The present study examined the relationships among gender stereotypes, sexism, and sexual harassment in online games, and further investigated how enhanced social presence contributes to intensifying the effects of gender stereotypes and sexism on sexual harassment. An online survey was conducted among 521 young male Korean gamers who regularly play two genres of online games: role-playing games and first-person shooter games. The results of moderated-mediation analyses using Hayes PROCESS macro models confirmed that gender stereotypes had significant effects on hostile and benevolent in-game sexism. A significant interaction was also observed between in-game sexism and social presence in predicting sexual harassment in online games. The findings from this study confirm the role of social presence as an amplifier that reinforces gender stereotypes and discrimination in competitive and violent online game environments.
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Acoso Sexual , Juegos de Video , Humanos , Masculino , Femenino , Sexismo , Estereotipo , República de CoreaRESUMEN
Diabetes and prediabetes (called abnormal glucose regulation (AGR)) are adverse health effects associated with exposure to pesticides. However, there are few epidemiological studies on the relationship between pesticide use and the incidence of AGR. We examined the causal relationship between pesticide use and AGR incidence in a rural population using data from a Korean Farmers' Cohort study of 1076 participants. Poisson regression with robust error variance was used to calculate the relative risks (RR) and 95% confidence intervals (CI) to estimate the relationship between pesticide exposure and AGR. The incidence of AGR in the pesticide-exposed group was 29.1%. Pesticide use increased the RR of AGR (RR 1.32, 95% CI 1.03-1.69). We observed a low-dose effect related to exposure of pesticides to AGR and a U-shaped dose-response relationship in men. Pesticide exposure is related to the incidence of AGR, and the causal relationship differs between men and women.
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Exposición Profesional , Plaguicidas , Agricultura , Estudios de Cohortes , Femenino , Glucosa , Humanos , Incidencia , Masculino , Exposición Profesional/efectos adversos , Plaguicidas/toxicidad , Estudios RetrospectivosRESUMEN
Chromosome loops shift dynamically during development, homeostasis, and disease. CCCTC-binding factor (CTCF) is known to anchor loops and construct 3D genomes, but how anchor sites are selected is not yet understood. Here, we unveil Jpx RNA as a determinant of anchor selectivity. Jpx RNA targets thousands of genomic sites, preferentially binding promoters of active genes. Depleting Jpx RNA causes ectopic CTCF binding, massive shifts in chromosome looping, and downregulation of >700 Jpx target genes. Without Jpx, thousands of lost loops are replaced by de novo loops anchored by ectopic CTCF sites. Although Jpx controls CTCF binding on a genome-wide basis, it acts selectively at the subset of developmentally sensitive CTCF sites. Specifically, Jpx targets low-affinity CTCF motifs and displaces CTCF protein through competitive inhibition. We conclude that Jpx acts as a CTCF release factor and shapes the 3D genome by regulating anchor site usage.
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Factor de Unión a CCCTC/metabolismo , Cromosomas/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Sitios de Unión , Línea Celular , Células Madre Embrionarias , Ratones , Unión ProteicaRESUMEN
How allelic asymmetry is generated remains a major unsolved problem in epigenetics. Here we model the problem using X-chromosome inactivation by developing "BioRBP", an enzymatic RNA-proteomic method that enables probing of low-abundance interactions and an allelic RNA-depletion and -tagging system. We identify messenger RNA-decapping enzyme 1A (DCP1A) as a key regulator of Tsix, a noncoding RNA implicated in allelic choice through X-chromosome pairing. DCP1A controls Tsix half-life and transcription elongation. Depleting DCP1A causes accumulation of X-X pairs and perturbs the transition to monoallelic Tsix expression required for Xist upregulation. While ablating DCP1A causes hyperpairing, forcing Tsix degradation resolves pairing and enables Xist upregulation. We link pairing to allelic partitioning of CCCTC-binding factor (CTCF) and show that tethering DCP1A to one Tsix allele is sufficient to drive monoallelic Xist expression. Thus, DCP1A flips a bistable switch for the mutually exclusive determination of active and inactive Xs.
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Endorribonucleasas/metabolismo , ARN/metabolismo , Transactivadores/metabolismo , Cromosoma X/metabolismo , Alelos , Animales , Factor de Unión a CCCTC/metabolismo , Línea Celular , Femenino , Regulación del Desarrollo de la Expresión Génica/fisiología , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/metabolismo , Transcripción Genética/fisiología , Regulación hacia Arriba/fisiología , Inactivación del Cromosoma X/fisiologíaRESUMEN
The mouse lncRNA Jpx has been shown as an essential regulator in X-chromosome inactivation (XCI). Jpx RNA activates Xist expression through its trans-acting ability to evict CTCF from Xist promoter. Karner et al. (2019) reveals the intriguing finding that human JPX and mouse Jpx are functionally conserved although they have low similarity in the primary sequence and the secondary structure. This study provides an excellent model for studying lncRNA's evolution and epigenetic function.
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ARN Largo no Codificante , Animales , Humanos , Ratones , Regiones Promotoras Genéticas , Inactivación del Cromosoma XRESUMEN
This study explores the roles of perceived message importance, health anxiety, and health literacy in the relationship between message factors (message label and message valence) and behavioral intentions for rumor verification and sharing. 660 Twitter users responded to unverified information regarding the influenza vaccine. A 3 (label: none vs. news vs. rumor) × 2 (valence: positive vs. negative) online semi-experiment, with a survey to measure health anxiety and health literacy, showed the following results: First, perceived message importance mediated the relationship between message factors and behavioral intentions: only in the condition of the negative message, participants considered a news-labeled message more important than a rumor-labeled or a no-label message. Perceived message importance was associated with intentions to verify and share the message. Second, health anxiety interacted with perceived message importance only when predicting an intention to share the message. Last, healthy literacy interacted with perceived message importance when predicting intentions to both verify and share the message. The results will provide implications for health communication research and practices, especially on managing and controlling rumor dissemination on social media.
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Ansiedad/psicología , Actitud Frente a la Salud , Comunicación en Salud , Alfabetización en Salud/estadística & datos numéricos , Medios de Comunicación Sociales/estadística & datos numéricos , Adulto , Femenino , Humanos , Intención , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
Mammalian chromosomes are partitioned into A/B compartments and topologically associated domains (TADs). The inactive X (Xi) chromosome, however, adopts a distinct conformation without evident compartments or TADs. Here, through exploration of an architectural protein, structural-maintenance-of-chromosomes hinge domain containing 1 (SMCHD1), we probe how the Xi is reconfigured during X chromosome inactivation. A/B compartments are first fused into "S1" and "S2" compartments, coinciding with Xist spreading into gene-rich domains. SMCHD1 then binds S1/S2 compartments and merges them to create a compartment-less architecture. Contrary to current views, TADs remain on the Xi but in an attenuated state. Ablating SMCHD1 results in a persistent S1/S2 organization and strengthening of TADs. Furthermore, loss of SMCHD1 causes regional defects in Xist spreading and erosion of heterochromatic silencing. We present a stepwise model for Xi folding, where SMCHD1 attenuates a hidden layer of Xi architecture to facilitate Xist spreading.
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Proteínas Cromosómicas no Histona/metabolismo , Cromosomas de los Mamíferos/química , Inactivación del Cromosoma X , Alelos , Animales , Línea Celular , Proteínas Cromosómicas no Histona/genética , Cromosomas de los Mamíferos/metabolismo , Metilación de ADN , Femenino , Heterocromatina/metabolismo , Histonas/genética , Histonas/metabolismo , Masculino , Ratones , Células Madre Embrionarias de Ratones/citología , Células Madre Embrionarias de Ratones/metabolismo , Análisis de Componente Principal , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Through an integration of genomic and proteomic approaches to advance understanding of long noncoding RNAs, we investigate the function of the telomeric transcript, TERRA. By identifying thousands of TERRA target sites in the mouse genome, we demonstrate that TERRA can bind both in cis to telomeres and in trans to genic targets. We then define a large network of interacting proteins, including epigenetic factors, telomeric proteins, and the RNA helicase, ATRX. TERRA and ATRX share hundreds of target genes and are functionally antagonistic at these loci: whereas TERRA activates, ATRX represses gene expression. At telomeres, TERRA competes with telomeric DNA for ATRX binding, suppresses ATRX localization, and ensures telomeric stability. Depleting TERRA increases telomerase activity and induces telomeric pathologies, including formation of telomere-induced DNA damage foci and loss or duplication of telomeric sequences. We conclude that TERRA functions as an epigenomic modulator in trans and as an essential regulator of telomeres in cis.
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ADN Helicasas/metabolismo , Proteínas Nucleares/metabolismo , Proteoma/metabolismo , ARN Largo no Codificante/metabolismo , Telómero/metabolismo , Animales , Ensayo de Cambio de Movilidad Electroforética , Ratones , Motivos de Nucleótidos , Células Madre/metabolismo , Telomerasa/metabolismo , Proteína Nuclear Ligada al Cromosoma XRESUMEN
In mammals, homologous chromosomes rarely pair outside meiosis. One exception is the X chromosome, which transiently pairs during X-chromosome inactivation (XCI). How two chromosomes find each other in 3D space is not known. Here, we reveal a required interaction between the X-inactivation center (Xic) and the telomere in mouse embryonic stem (ES) cells. The subtelomeric, pseudoautosomal regions (PARs) of the two sex chromosomes (X and Y) also undergo pairing in both female and male cells. PARs transcribe a class of telomeric RNA, dubbed PAR-TERRA, which accounts for a vast majority of all TERRA transcripts. PAR-TERRA binds throughout the genome, including to the PAR and Xic. During X-chromosome pairing, PAR-TERRA anchors the Xic to the PAR, creating a 'tetrad' of pairwise homologous interactions (Xic-Xic, PAR-PAR, and Xic-PAR). Xic pairing occurs within the tetrad. Depleting PAR-TERRA abrogates pairing and blocks initiation of XCI, whereas autosomal PAR-TERRA induces ectopic pairing. We propose a 'constrained diffusion model' in which PAR-TERRA creates an interaction hub to guide Xic homology searching during XCI.
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Emparejamiento Cromosómico , Proteínas de Unión al ADN/metabolismo , Regiones Pseudoautosómicas/metabolismo , Cromosomas Sexuales/metabolismo , Factores de Transcripción/metabolismo , Inactivación del Cromosoma X , Animales , Ratones , Transcripción GenéticaRESUMEN
This study aims to understand the impact of descriptive social norms on message believability and transmission and its underlying mechanism on Twitter. Using two types of information (i.e., news and rumor) presented as a tweet message, the influence of the number of retweets as a normative cue was tested. A result of an online experiment with 639 Twitter users suggests that regardless of the label of the information, message believability and intention to share were stronger for a tweet with a high number of retweets. The mediation test showed that the presumption that a message is believable to others mediates the relationship between a high number of retweets and message believability.
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Difusión de la Información , Medios de Comunicación Sociales/estadística & datos numéricos , Red Social , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Tooth development involves sequential interactions between dental epithelial and mesenchymal cells. Our previous studies demonstrated that preameloblast-conditioned medium (PA-CM) induces the odontogenic differentiation of human dental pulp cells (hDPCs), and the novel protein Cpne7 in PA-CM was suggested as a candidate signaling molecule. In the present study, we investigated biological function and mechanisms of Cpne7 in regulation of odontoblast differentiation. Cpne7 was expressed in preameloblasts and secreted extracellularly during ameloblast differentiation. After secretion, Cpne7 protein was translocated to differentiating odontoblasts. In odontoblasts, Cpne7 promoted odontoblastic markers and the expression of Dspp in vitro. Cpne7 also induced odontoblast differentiation and promoted dentin/pulp-like tissue formation in hDPCs in vivo. Moreover, Cpne7 induced differentiation into odontoblasts of non-dental mesenchymal stem cells in vitro, and promoted formation of dentin-like tissues including the structure of dentinal tubules in vivo. Mechanistically, Cpne7 interacted with Nucleolin and modulated odontoblast differentiation via the control of Dspp expression. These results suggest Cpne7 is a diffusible signaling molecule that is secreted by preameloblasts, and regulates the differentiation of mesenchymal cells of dental or non-dental origin into odontoblasts.
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Ameloblastos/metabolismo , Diferenciación Celular , Proteínas de la Membrana/metabolismo , Células Madre Mesenquimatosas/citología , Odontoblastos/citología , Animales , Línea Celular , Pulpa Dental/citología , Dentina/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Humanos , Células Madre Mesenquimatosas/metabolismo , Ratones , Odontoblastos/metabolismo , Fosfoproteínas/metabolismo , Unión Proteica , Transporte de Proteínas , Proteínas de Unión al ARN/metabolismo , Sialoglicoproteínas/metabolismo , NucleolinaRESUMEN
In the context of healthy snacking, this study examines whether the quality of mental imagery determines the effectiveness of combining the implementation intention (II) intervention with mental imagery. This study further explores whether providing narrative healthy snacking scenarios prior to forming an II enhances people's mental imagery experience when they are not motivated to snack healthfully. A 2 × 2 factorial design was employed to test the main effect of providing healthy snacking scenarios prior to II formation, and whether such effect depends on people's motivation level. The results from the experiment (N =148) showed significant main as well as interaction effects of the manipulation (with vs. without reading healthy snacking scenarios prior to II formation) and motivation level on ease and vividness of mental imagery. The regression model with the experiment and follow-up survey data (n = 128) showed a significant relationship between ease of mental imagery and actual snacking behavior after controlling for habit strength. The findings suggest that adding a narrative message to the II intervention can be useful, especially when the intervention involves mental imagery and invites less motivated people.
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Conductas Relacionadas con la Salud , Comunicación en Salud/métodos , Intención , Bocadillos/psicología , Estudiantes/psicología , Adolescente , Adulto , Conducta Alimentaria , Femenino , Humanos , Masculino , Medio Oeste de Estados Unidos , Motivación , Universidades , Adulto JovenRESUMEN
This study evaluated a community-based and social marketing healthy corner store program (FIT store) to improve the affordability and availability of healthy foods in low-income, urban, and ethnically diverse neighborhoods in Michigan. The Nutrition Environment Measures Survey in Stores data were analyzed for the FIT (N = 4) stores. Two cross-sectional surveys were conducted among the FIT store customers before (N = 401) and after (N = 318) the intervention. Three FIT stores improved their total Nutrition Environment Measures Survey in Stores availability score from before to after the intervention. A significantly higher level of FIT awareness and monthly bean and nut consumption was reported in the postintervention.
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Comercio/normas , Etnicidad/estadística & datos numéricos , Abastecimiento de Alimentos/normas , Promoción de la Salud/métodos , Pobreza , Características de la Residencia/estadística & datos numéricos , Adulto , Comercio/economía , Estudios Transversales , Femenino , Abastecimiento de Alimentos/economía , Abastecimiento de Alimentos/estadística & datos numéricos , Humanos , Masculino , Michigan , Persona de Mediana Edad , Encuestas Nutricionales , Medio Social , Mercadeo Social , Población Urbana , Adulto JovenRESUMEN
BACKGROUND: In efforts to curb and prevent youth smoking, school tobacco policies have become an important and effective strategy. This study explores the degrees and types of tobacco-free school policy (TFSP) enforcement that are associated with adolescent smoking. METHODS: A multilevel analysis was performed using 983 students who are nested in 14 schools. The individual-level data are drawn from the 2009 Michigan Youth Risk Behavior Survey. The school-level data are drawn from the 2008 School Health Profiles survey. RESULTS: Two factors are associated with lower adolescent smoking: greater punishment for TFSP violation and more tobacco control communication efforts. By contrast, the factors associated with higher adolescent smoking are designation of a tobacco-free school zone and school-level smoking. CONCLUSIONS: This study theoretically and methodologically guides researchers to test TFSP effectiveness in other states. Three strategic implications emerge: (1) schools should provide a consistent antismoking message in smoke-free environments; (2) schools should integrate TFSP into a comprehensive tobacco control initiative, including community-wide tobacco control programs and messages; and (3) the way a specific TFSP is promoted and communicated could determine how effective it is.
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Política de Salud , Promoción de la Salud/métodos , Servicios de Salud Escolar/organización & administración , Prevención del Hábito de Fumar , Estudiantes/estadística & datos numéricos , Contaminación por Humo de Tabaco/prevención & control , Adolescente , Conducta del Adolescente/psicología , Femenino , Humanos , Masculino , Michigan , Política OrganizacionalRESUMEN
Excess oxidant can promote inflammatory responses. Moreover, chronic inflammation accompanied by oxidative stress is connected various steps involved in many diseases. From the aspect, we investigated an antioxidant peptide to prevent inflammatory response against oxidant overexpression. To prepare the peptide, eight proteases were employed for enzymatic hydrolysis, and the antioxidant properties of the hydrolysates were investigated using free radical scavenging activity by electron spin resonance (ESR) spectrometry. Papain hydrolysates, which showed clearly superior free radical scavenging activity, were further purified using consecutive chromatographic methods. Finally, a novel antioxidant peptide was obtained, and the sequence was identified as Ser-Leu-Pro-Ile-Gly-Leu-Met-Ile-Ala-Met at N-terminal. Oral administration of the peptide to mice effectively inhibited malondialdehyde (MDA) levels in a thiobarbituric acid reactive substances (TBARS) assay, and we also confirmed the antioxidative enzyme activities in superoxide dismutase (SOD) and glutathione-s-transferase (GST) assays. This is the first report of an antioxidant peptide derived from the hydrolysate of Mytilus coruscus, and also these results suggest that the peptide possesses potent antioxidant activity, and potential to enhance anti-inflammatory response.
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Antioxidantes/metabolismo , Depuradores de Radicales Libres/metabolismo , Mytilus/metabolismo , Péptidos/aislamiento & purificación , Animales , Antioxidantes/química , Femenino , Glutatión Transferasa/metabolismo , Malondialdehído/metabolismo , Ratones , Datos de Secuencia Molecular , Mytilus/química , Mytilus/genética , Oxidación-Reducción , Péptidos/química , Péptidos/genética , Péptidos/metabolismo , República de Corea , Análisis de Secuencia de Proteína , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismoRESUMEN
This study explicates mechanisms of media campaign effectiveness in the context of children's physical activity. The authors' model expands the theory of planned behavior by integrating injunctive and descriptive norms into its normative mechanism. Analysis of a 3-wave nationally representative evaluation survey among 1,623 tweens indicates that campaign exposure is significantly related, but only indirectly, to both physical activity intention and physical activity behavior. Instead, campaign exposure seems more strongly related to perceived behavioral control and attitudes toward physical activity. By contrast, perceived behavioral control and descriptive norms are strongly related to behavioral intention. The findings suggest that integrating normative mechanisms with the theory of planned behavior can improve efforts to predict and explain a health behavior.
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Conducta Infantil/psicología , Promoción de la Salud , Intención , Medios de Comunicación de Masas , Actividad Motora , Teoría Psicológica , Valores Sociales , Adolescente , Niño , Femenino , Humanos , Estudios Longitudinales , Masculino , Modelos Psicológicos , Evaluación de Programas y Proyectos de Salud , Estados UnidosRESUMEN
BACKGROUNDS & AIMS: The clinical severity of cirrhosis varies widely. We investigated whether histological sub-classification of cirrhosis using the Laennec system can discriminate different outcomes among patients with cirrhosis. METHODS: One hundred and seventy-five patients with chronic liver disease who underwent liver biopsy and showed stage 3 or 4 fibrosis between January 2001 and December 2008 were prospectively enrolled. Cirrhosis was sub-classified into three groups (4A, 4B, and 4C) according to the Laennec system. The end point was liver-related event (LRE) occurrence, including decompensation, hepatocellular carcinoma, and liver-related death. RESULTS: The median age of the patients (110 men, 65 women) was 55 years. Stages 3, 4A, 4B, and 4C were identified in 46 (26.3%), 16 (9.1%), 82 (46.9%), and 31 (17.7%) patients, respectively. During the follow-up period, LREs occurred in 32 (18.3%) patients: 4 (8.7%) with stage 3, 2 (12.5%) with stage 4A, 17 (20.7%) with stage 4B, and 9 (29.0%) with stage 4C. In a multivariate analysis, histological sub-classification of cirrhosis independently predicted LRE occurrence. While patients with stage 4A tended to be at higher risk of LRE occurrence than those with stage 3, patients with stages 4B and 4C had significantly higher risks of LRE occurrence, with hazard ratios of 6.158 (p=0.016) and 8.945 (p=0.004), respectively. CONCLUSIONS: Histological sub-classification of cirrhosis using the Laennec system can be used to assess the risk of LRE occurrence among patients with cirrhosis. Our study provides a solid basis for further studies of non-invasive methods for monitoring the risk of LRE occurrence and will help physicians to establish optimum treatment strategies.
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Carcinoma Hepatocelular/etiología , Cirrosis Hepática/clasificación , Cirrosis Hepática/patología , Fallo Hepático/etiología , Neoplasias Hepáticas/etiología , Índice de Severidad de la Enfermedad , Adolescente , Adulto , Anciano , Alanina Transaminasa/sangre , Aspartato Aminotransferasas/sangre , Bilirrubina/sangre , Biopsia , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Estimación de Kaplan-Meier , Cirrosis Hepática/complicaciones , Fallo Hepático/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recuento de Plaquetas , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Tiempo de Protrombina , Medición de Riesgo , Albúmina Sérica , Adulto Joven , alfa-FetoproteínasRESUMEN
During tooth development and tumorigenesis, the odontogenic ameloblast-associated protein (ODAM) is involved in cellular differentiation and matrix protein production. However, the precise function of ODAM remains largely unknown. To suggest new functional roles of ODAM, we investigated the cellular expression and subcellular localization of ODAM in tooth and cancer cells. ODAM was expressed in ameloblasts, odontoblasts, and osteoblasts in vivo and in vitro. Furthermore, ODAM was localized in both the nucleus and cytoplasm of MMP-20 expressing ameloblasts and odontoblasts, but only in the cytoplasm of non-MMP-20 expressing osteoblasts. The extracellular secretion of ODAM was not observed in odontoblasts and osteoblasts, but was seen in ameloblasts. In addition, ODAM was discovered in the nucleus, cytoplasm, and extracellular matrix of various cancer cells. These results suggest that the expression pattern and subcellular localization of ODAM is highly variable and dependent on cell types and their differentiation states, and that functional correlations exist between ODAM and MMP-20. This study provides the first evidence for ODAM in multiple cellular compartments of differentiating odontogenic and cancer cell lines with important functional implications.
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Ameloblastos/metabolismo , Proteínas Portadoras/metabolismo , Regulación Neoplásica de la Expresión Génica , Odontoblastos/metabolismo , Osteoblastos/metabolismo , Proteínas/metabolismo , Ameloblastos/citología , Amiloide , Animales , Proteínas Portadoras/genética , Diferenciación Celular/genética , Línea Celular Tumoral , Núcleo Celular/metabolismo , Femenino , Mucosa Gástrica/metabolismo , Células HeLa , Humanos , Péptidos y Proteínas de Señalización Intracelular , Riñón/metabolismo , Células MCF-7 , Metaloproteinasa 20 de la Matriz/genética , Metaloproteinasa 20 de la Matriz/metabolismo , Ratones , Proteínas de Neoplasias , Odontoblastos/citología , Odontogénesis/genética , Osteoblastos/citología , Ovario/metabolismo , Proteínas/genéticaRESUMEN
Zinc is trace element essential for diverse metabolic and cellular signaling pathways for the growth, development, and maintenance. Zinc deficiency is involved in bone malformations and oral disease. Mice deficient in zinc transporter Zip13 show connective tissue and skeletal disorders, abnormal incisor teeth, and reduced root dentin formation in the molar teeth and share a morphologically similar phenotype to nuclear factor I-C (NFI-C)-deficient mice. However, the precise function of zinc in NFI-C signaling-mediated odontoblast differentiation and dentin formation remains unclear. Here, we show that zinc stimulated the expression of metal transcription factor-1, but decreased NFI-C expression in odontoblastic MDPC-23 cells. Zinc also enhanced the phosphorylation of Smad2/3 (p-Smad2/3) and increased the binding efficiency of NFI-C and p-Smad2/3 in the cytoplasm. In contrast, zinc deficiency resulted in the accumulation of NFI-C into nucleus. Consequently, NFI-C had the biologic properties of a transcription factor, including DNA binding affinity for metallothionein-1 and the dentin sialophosphoprotein (DSPP) promoter, and transcriptional activation of the DSPP gene. Furthermore, zinc deficiency condition promoted DSPP expression in odontoblasts and dentin mineralization, while zinc sufficiency condition decreased DSPP expression and slightly delayed dentin mineralization. These data suggest that zinc equilibrium is required for odontoblast differentiation and dentin formation during dentinogenesis through the nuclear accumulation and modulation of NFI-C.