IL-35 subunit EBI3 alleviates bleomycin-induced pulmonary fibrosis via suppressing DNA enrichment of STAT3.

Chen, Donghong; Zheng, Guofeng; Yang, Qing; Luo, Le; Shen, Jinglian

Chen, Donghong; Zheng, Guofeng; Yang, Qing; Luo, Le; Shen, Jinglian.

Afiliación

Chen D; Department of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University/China Medical University, Seven South Road, Shenyang, 110005, Liaoning, China.
Zheng G; Department of Respiratory Medicine, The Fourth Affiliated Hospital of China Medical University/China Medical University, Seven South Road, Shenyang, 110005, Liaoning, China.
Yang Q; Emergency Department, The Fourth Affiliated Hospital of China Medical University/China Medical University, Seven South Road, Shenyang, 110005, Liaoning, China.
Luo L; Shanghai Yunhao Biotech Center, Shanghai, 200000, China.
Shen J; Emergency Department, The Fourth Affiliated Hospital of China Medical University/China Medical University, Seven South Road, Shenyang, 110005, Liaoning, China. jlshen@cmu.edu.cn.

Respir Res ; 22(1): 280, 2021 Oct 28.

Article en En | MEDLINE | ID: mdl-34711217

RESUMEN

BACKGROUND: IL-35 subunit EBI3 is up-regulated in pulmonary fibrosis tissues. In this study, we investigated the pathological role of EBI3 in pulmonary fibrosis and dissected the underlying molecular mechanism. METHODS: Bleomycin-induced pulmonary fibrosis mouse model was established, and samples were performed gene expression analyses through RNAseq, qRT-PCR and Western blot. Wild type and EBI3 knockout mice were exposed to bleomycin to investigate the pathological role of IL-35, via lung function and gene expression analyses. Primary lung epithelial cells were used to dissect the regulatory mechanism of EBI3 on STAT1/STAT4 and STAT3. RESULTS: IL-35 was elevated in both human and mouse with pulmonary fibrosis. EBI3 knockdown aggravated the symptoms of pulmonary fibrosis in mice. EBI3 deficiency enhanced the expressions of fibrotic and extracellular matrix-associated genes. Mechanistically, IL-35 activated STAT1 and STAT4, which in turn suppressed DNA enrichment of STAT3 and inhibited the fibrosis process. CONCLUSION: IL-35 might be one of the potential therapeutic targets for bleomycin-induced pulmonary fibrosis.

Asunto(s)

Células Epiteliales/metabolismo; Pulmón/metabolismo; Antígenos de Histocompatibilidad Menor/metabolismo; Fibrosis Pulmonar/metabolismo; Receptores de Citocinas/metabolismo; Factor de Transcripción STAT3/metabolismo; Adulto; Animales; Sitios de Unión; Bleomicina; Estudios de Casos y Controles; Células Cultivadas; Modelos Animales de Enfermedad; Células Epiteliales/efectos de los fármacos; Células Epiteliales/patología; Proteínas de la Matriz Extracelular/genética; Proteínas de la Matriz Extracelular/metabolismo; Femenino; Regulación de la Expresión Génica; Humanos; Interleucina-6/farmacología; Interleucinas/genética; Interleucinas/metabolismo; Interleucinas/farmacología; Pulmón/efectos de los fármacos; Pulmón/patología; Masculino; Ratones Endogámicos C57BL; Ratones Noqueados; Persona de Mediana Edad; Antígenos de Histocompatibilidad Menor/genética; Fosforilación; Fibrosis Pulmonar/inducido químicamente; Fibrosis Pulmonar/patología; Receptores de Citocinas/genética; Factor de Transcripción STAT1/metabolismo; Factor de Transcripción STAT4/metabolismo; Adulto Joven

Palabras clave

DNA enrichment; IL-35; Pulmonary fibrosis; STAT1/STAT4; STAT3

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fibrosis Pulmonar / Antígenos de Histocompatibilidad Menor / Receptores de Citocinas / Células Epiteliales / Factor de Transcripción STAT3 / Pulmón Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Respir Res Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

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