％0期刊文章％A Boutanquoi，Pierre-Marie％A Burgy，Olivier％A Beltramo，Guillaume％A Bellaye，Pierre-Simon％A Dondaine，Lucile％A Marcion，Guillaume％A Pommerolle，Lenny％A Vadel，Aurélie％aSpanaard，Maximilien％A Demidov，Oleg％A mailleux，Arnaud％A Crestani，Bruno％A Kolb，Martin％A Garrido，Carmen％Goirand，Françoise％Bonniaud，Philippe％T Trim33通过损害TGF-β1信号来预防肺纤维化％D 2020％R 10.1183 / 13993003.01346-2019％J欧洲呼吸轴颈％P 1901346％V 55％N 6％X背景发作性肺纤维化（IPF）是一种毁灭性的疾病，其特征在于肺中肌纤维细胞增殖和异常细胞外基质积累。转化生长因子（TGF）-β1引发涉及Smad途径和小型热休克蛋白B5（Hspb5）的关键突触式信号传导。据报道，含三方用基序的33（Trim33）对TGF-β/ Smad信号传导进行负调节，但其在纤维发生中的作用仍然是未知的。本研究的目的是阐明Trim33在IPF中的作用。方法在IPF患者的肺部和啮齿动物纤维化模型中评估了TRIM33表达。骨髓衍生的巨噬细胞（BMDM），原发性肺成纤维细胞和3D肺组织切片与TRIM33氟化小鼠分离，并用TGF-β1或BLEOMYCIN（BLM）培养。然后通过腺病毒CRE重组酶（Adcre）抑制Trim33表达。在血吞噬特异性的TREM33敲除小鼠中评价肺纤维化，并在接受Adcre和Blm的Trim33-氟化小鼠中进行肿瘤内肿瘤瘤。结果在IPF患者和啮齿动物纤维化肺中的肺泡巨噬细胞和成纤维细胞中过表达。Trim33在BMDM中抑制在BLM处理时增加TGF-β1分泌。 Haematopoietic-specific Trim33 knockout sensitised mice to BLM-induced fibrosis. In primary lung fibroblasts and 3D lung tissue slices, Trim33 deficiency increased expression of genes downstream of TGF-β1. In mice, AdCre-Trim33 inhibition worsened BLM-induced fibrosis. In vitro, HSPB5 was able to bind directly to TRIM33, thereby diminishing its protein level and TRIM33/SMAD4 interaction.Conclusion Our results demonstrate a key role of TRIM33 as a negative regulator of lung fibrosis. Since TRIM33 directly associates with HSPB5, which impairs its activity, inhibitors of TRIM33/HSPB5 interaction may be of interest in the treatment of IPF.TRIM33 has a protective role against fibrogenesis, inhibiting the TGF-β1 pathway through a direct association with HSPB5. Interactions between TRIM33, SMAD4 and HSPB5 may represent key targets to prevent the progression of pulmonary fibrosis. http://bit.ly/3aVCuxc %U //www.qdcxjkg.com/content/erj/55/6/1901346.full.pdf