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| 1 | LncRNA DACH1 protects against pulmonary fibrosis by binding to SRSF1 to suppress CTNNB1 accumulation显示文摘Idiopathic pulmonary fibrosis(IPF)is a progressive disease with unknown etiology and limited therapeutic options.Activation of fibroblasts is a prominent feature of pulmonary fibrosis.Here we report that lncRNA DACH1(dachshund homolog 1)is downregulated in the lungs of IPF patients and in an experimental mouse model of lung fibrosis.LncDACH1 knockout mice develop spontaneous pulmonary fibrosis,whereas overexpression of LncDACH1 attenuated TGF-β1-induced aberrant activation,collagen deposition and differentiation of mouse lung fibroblasts.Similarly,forced expression of LncDACH1 not only prevented bleomycin(BLM)-induced lung fibrosis,but also reversed established lung fibrosis in a BLM model.Mechanistically,LncDACH1 binding to the serine/arginine-rich splicing factor 1(SRSF1)protein decreases its activity and inhibits the accumulation of Ctnnb1.Enhanced expression of SRSF1 blocked the anti-fibrotic effect of LncDACH1 in lung fibroblasts.Furthermore,loss of LncDACH1 promoted proliferation,differentiation,and extracellular matrix(ECM)deposition in mouse lung fibroblasts,whereas such effects were abolished by silencing of Ctnnb1.In addition,a conserved fragment of LncDACH1 alleviated hyperproliferation,ECM deposition and differentiation of MRC-5 cells driven by TGF-β1.Collectively,LncDACH1 inhibits lung fibrosis by interacting with SRSF1 to suppress CTNNB1 accumulation,suggesting that LncDACH1 might be a potential therapeutic target for pulmonary fibrosis. | Jian Sun Tongzhu Jin Zhihui Niu Jiayu Guo Yingying Guo Ruoxuan Yang Qianqian Wang Huiying Gao Yuhan Zhang Tianyu Li Wenxin He Zhixin Li Wenchao Ma Wei Su Liangliang Li Xingxing Fan Hongli Shan Haihai Liang | 2022 | Acta Pharmaceutica Sinica B2022，12，9： | 1 |
| 2 | 转录因子C/EBPβ在肺部疾病中的分子机制研究进展显示文摘CCAAT增强子结合蛋白β(C/EBPβ)作为肝脏、气道上皮和脂肪组织发育所必需的核转录因子,在细胞增殖、凋亡和分化相关的生理过程中发挥重要作用。然而,在肺部疾病中,C/EBPβ的上调通过调控下游一系列基因转录,激活与炎症反应、上皮-间充质转化、细胞增殖与侵袭、免疫反应和血管生成相关的信号通路,促进疾病的发展。靶向C/EBPβ可能是潜在的肺部疾病治疗策略。现对C/EBPβ及相关信号通路在肺部感染、哮喘、慢性阻塞性肺疾病、肺损伤、肺纤维化和肺癌中的调控作用进行归纳综述,以期为肺部疾病的精准治疗提供理论依据。 | 温海云 罗亚岚 葛鹏 兰博文 董宣池 张桂信 陈海龙 | 2022 | 中华危重病急救医学2022，34，8： | 0 |
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