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Using forward and reverse genetics and global gene expression analyses, we explored the crosstalk between the IκB kinase β (IKKβ) and the transforming growth factor β (TGFβ) signaling pathways. We show that in vitro ablation of Ikkβ in fibroblasts led to progressive ROS accumulation and TGFβ activation, and ultimately accelerated cell migration, fibroblast-myofibroblast transformation and senescence. Mechanistically, the basal IKKβ activity was required for anti-oxidant gene expression and redox homeostasis. Lacking this activity, IKKβ-null cells showed ROS accumulation and activation of stress-sensitive transcription factor AP-1/c-Jun. AP-1/c-Jun activation led to up-regulation of the Tgfβ2 promoter, which in turn further potentiated intracellular ROS through the induction of NADPH oxidase (NOX). These data suggest that by blocking the autocrine amplification of a ROS-TGFβ loop IKKβ plays a crucial role in the prevention of fibroblast-myofibroblast transformation and senescence.
Asunto(s)
Animales , Ratones , Adenoviridae , Genética , Comunicación Autocrina , Fisiología , Línea Celular , Movimiento Celular , Senescencia Celular , Vectores Genéticos , Genética , Metabolismo , Quinasa I-kappa B , Genética , Metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos , Metabolismo , Miofibroblastos , Biología Celular , Metabolismo , NADPH Oxidasas , Metabolismo , Estrés Oxidativo , Regiones Promotoras Genéticas , Especies Reactivas de Oxígeno , Metabolismo , Transducción de Señal , Superóxido Dismutasa , Genética , Metabolismo , Factor de Transcripción AP-1 , Metabolismo , Factor de Crecimiento Transformador beta , Genética , Metabolismo , Regulación hacia ArribaRESUMEN
Objective To translate the Work Limitations Questionnaire and examine its reliability and validity,and explore its applicability at home.Methods 300 nurses were surveyed with the Chinese version of the Work Limitations Questionnaire by convenience sampling; and internal consistency reliability,test-retest reliability,construct validity and criterion validity were applied to evaluate the questionnaire.Results The Cronbach α coefficients of the time managing scale,physical scale,mental-interpersonal scale,output scale and total questionnaire were 0.882,0.864,0.913,0.839 and 0.922 respectively;and their test-retest reliability coefficients were 0.857,0.837,0.871,0.803 and 0.893 respectively.Four common factors were abstracted by using factor analysis,with the cumulative variance contribution rate at 61.293％.Using SF-36 as an external criterion,the correlation coefficients of the WLQ scores with the physical function dimension and mental health dimension of the SF-36 were-0.24 and-0.33.Conclusions The reliability and validity of the questionnaire is reasonable.So this questionnaire can be used to measure employee's presenteeism.
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Objective To investigate the job burnout status of nurses in a third-grade and A-level general hospital in Zhengzhou,and analyze the relationship between job burnout and presenteeism.Methods 300 nurses were surveyed with questionnaires by convenience sampling,including nurses' demographic data,Nurse Job Burnout Scale and Work Limitations Questionnaire.Results The scores in three dimensions of job burnout of nurses were respectively EE (25.92±11.56) points,DP (10.63±6.82) points,and PA(26.30±9.11) points.The job burnout rate in nurses was 76.2％,the rates of low,moderate,and high degree of burnout were respectively 30.4％,28.7％,and 17.4％.The scores of presenteeism for low,moderate,and high degree of work limitations were respectively (2.29±1.60)points,(5.90±3.03)points,(7.89±3.12)points.Conclusions Nurses' burnout can results in presenteeism.The more serious job burnout is,the more critical the presenteeism is.