ty-jour t1 - trim33防止肺纤维化受损伤tgf-β1信号jf - 欧洲呼吸杂志jo - 欧元reshir j do - 10.1183/13993003.01346-2019 vl - 55是 - 6 sp - 1901346 Au - Boutanquoi，Pierre-Marie Au -Burgy，Olivier Au - Beltramo，Guillaume Au - Bellaye，Pierre-Simon Au - Dondaine，Lucile Au - Marcion，Guillaume Au - Pommerolle，Lenny Au - Vadel，AurélieAu - Spanard，Maximilien Au - Demidov，Oleg Au - Mailleux，ArnaudAu - Crestani，Bruno Au - Kolb，Martin Au - Garrido，Carmen Au - Goirand，FrançoiseAu - Bonniaud，Philippe Y1 - 2020/06/01 UR - //www.qdcxjkg.com/content/55/6/1901346.Abstract N2 - 背景表现性肺纤维化（IPF）是一种毁灭性的疾病，其特征在于肺中的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 inhibition in BMDM increased TGF-β1 secretion upon BLM treatment. 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 ER -