title: A novel role of Yin-Yang-1 in pulmonary tuberculosis through the regulation of the chemokine CCL4.
abstract: Mycobacterium tuberculosis (M. tb) is the etiological agent of pulmonary tuberculosis (TB); this disease remains a worldwide health problem. Yin-Yang-1 (YY1) plays a major role in the maintenance and progression of some pulmonary diseases, including pulmonary fibrosis. However, the role of YY1 in TB remains unknown. The aim of this study was to elucidate the role of YY1 in the regulation of CCL4 and its implication in TB. We determined whether YY1 regulates CCL4 using reporter plasmids, ChIP and siRNA assays. Immunohistochemistry and digital pathology were used to measure the expression of YY1 and CCL4 in a mouse model of TB. A retrospective comparison of patients with TB and control subjects was used to measure the expression of YY1 and CCL4 using tissue microarrays. Our results showed that YY1 regulates the transcription of CCL4; moreover, YY1, CCL4 and TGF-β were overexpressed in the lung tissues of mice with TB during the late stages of the disease and the tissues of TB patients. The expression of CCL4 and TGF-β correlated with YY1 expression. In conclusion, YY1 regulates CCL4 transcription; moreover, YY1 is overexpressed in experimental and human TB and is positively correlated with CCL4 and TGF-β expression. Therefore, treatments that decrease YY1 expression may be a new therapeutic strategy against TB.
authors.affiliation: Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico "Federico Gomez", Mexico City, Mexico; Programa de Doctorado en Ciencias Biomedicas, Facultad de Medicina, UNAM, Mexico City, Mexico.
authors.forename: Jesus F
authors.initials: JF
authors.lastname: Rangel-Santiago
authors.affiliation: Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico "Federico Gomez", Mexico City, Mexico.
authors.forename: Guillermina J
authors.initials: GJ
authors.lastname: Baay-Guzman
authors.affiliation: Servicio de Patologia, Hospital General de Mexico "Eduardo Liceaga", Facultad de Medicina de la UNAM, Mexico City, Mexico.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Duran-Padilla
authors.affiliation: Servicio de Patologia, Hospital General de Mexico "Eduardo Liceaga", Facultad de Medicina de la UNAM, Mexico City, Mexico.
authors.forename: Karla A
authors.initials: KA
authors.lastname: Lopez-Bochm
authors.affiliation: Servicio de Patologia, Hospital General de Mexico "Eduardo Liceaga", Facultad de Medicina de la UNAM, Mexico City, Mexico.
authors.forename: Beatriz L
authors.initials: BL
authors.lastname: Garcia-Romero
authors.affiliation: Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico "Federico Gomez", Mexico City, Mexico.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Hernandez-Cueto
authors.affiliation: Oncology Research Unit, Oncology Hospital, CMN SXXI, IMSS, Mexico City, Mexico.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Pantoja-Escobar
authors.affiliation: Oncology Research Unit, Oncology Hospital, CMN SXXI, IMSS, Mexico City, Mexico.
authors.forename: Mario I
authors.initials: MI
authors.lastname: Vega
authors.affiliation: Pathology Experimental Section, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", Mexico City, Mexico.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Hernandez-Pando
authors.affiliation: Unidad de Investigacion en Enfermedades Oncologicas, Hospital Infantil de Mexico "Federico Gomez", Mexico City, Mexico. Electronic address: shuertay@gmail.com.
authors.forename: Sara
authors.initials: S
authors.lastname: Huerta-Yepez
mesh_terms: D000818:Animals; D002460:Cell Line; D054407:Chemokine CCL4 / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D004195:Disease Models, Animal; D018450:Disease Progression; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000276:immunology / Q000382:microbiology*; D008297:Male; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000472:pathogenicity; D034622:RNA Interference; D012189:Retrospective Studies; D015398:Signal Transduction; D013997:Time Factors; D046888:Tissue Array Analysis; D014158:Transcription, Genetic; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology; D050986:YY1 Transcription Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: C066507:CCL4 protein, human; D054407:Chemokine CCL4; D016212:Transforming Growth Factor beta; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C494699:Yy1 protein, mouse
keywords: CCL4; TGF-β; Tuberculosis; Yin-Yang-1