TY - JOUR T1 - TRIM33防止肺纤维化通过削弱TGF-β1信号传导JF - 欧洲呼吸杂志JO - 欧洲呼吸j执行 - 10.1183 / 13993003.01346-2019 VL - 55 - 6 SP - 1901346 AU - Boutanquoi，皮尔 - 马里AU -Burgy，奥利维尔AU - Beltramo，纪尧姆AU - Bellaye，皮埃尔 - 西蒙AU - Dondaine，露西尔AU - 马吉安，纪尧姆AU - Pommerolle，莱尼AU - Vadel，的AurélieAU - Spanjaard，马克西米AU - 杰米多夫，奥列格AU - MAILLEUX，阿尔诺AU - Crestani，布鲁诺AU - 科尔布，马丁AU - 加里多，卡门AU - Goirand，弗朗索瓦丝AU - Bonniaud，菲利普Y1 - 2020年6月1日UR - //www.qdcxjkg.com/content/55/6/1901346.abstract N2 - 背景特发性肺纤维化（IPF）是一种破坏性的疾病，其特征在肺成肌纤维细胞增殖和异常的细胞外基质累积。转化生长因子（TGF）-β1发起键促纤维化信令涉及Smad通路和小热休克蛋白B5（HSPB5）。三方33（TRIM33）含序已上报负调控TGF-β/ Smad信号，但其纤维化的作用尚不清楚。这项研究的目的是阐明TRIM33的IPF.Methods TRIM33表达中的作用IPF患者和啮齿动物纤维化模型的肺部进行了评估。骨髓衍生的巨噬细胞（BMDM），原发性肺成纤维细胞和3D肺组织切片从Trim33-两侧装接loxP小鼠中分离的培养和用TGF-β1或博来霉素（BLM）。Trim33表达然后通过腺病毒Cre重组酶（AdCre）抑制。肺纤维化在特定的造血Trim33敲除小鼠和在接受AdCre和BLM intratracheally.Results TRIM33在IPF患者和啮齿动物的肺纤维化肺泡巨噬细胞和成纤维细胞中过表达Trim33-两侧装接loxP小鼠进行了评价。 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 -