Frontiers in Cell and Developmental Biology ( IF 5.5 ) Pub Date : 2020-12-10 , DOI: 10.3389/fcell.2020.587502 Wenxuan Hong , Ming Kong , Mengwen Qi , Hui Bai , Zhiwen Fan , Ziyu Zhang , Aijun Sun , Xiangshan Fan , Yong Xu
Fulminant hepatitis (FH) is a major cause of acute liver failure. Concanavalin A (ConA) belongs to the lectin family and is frequently used as an inducer of FH in animal models. ConA induced FH is characterized by massive accumulation of T lymphocytes in the liver. A host of chemoattractive substances are known to promote T cell homing to the liver during acute hepatitis. Here we investigated the involvement of Brahma-related gene 1 (BRG1), a chromatin remodeling protein, in FH. BRG1-flox mice were crossed to Alb-Cre mice to generate hepatocyte conditional BRG1 knockout (LKO) mice. The mice were peritoneally injected with a single dose of ConA to induce FH. BRG1 deficiency mitigated ConA-induced FH in mice. Consistently, there were fewer T lymphocyte infiltrates in the LKO livers compared to the wild type (WT) livers paralleling downregulation of T cell specific cytokines. Further analysis revealed that BRG1 deficiency repressed the expression of several chemokines critical for T cell homing including nephronectin (Npnt). BRG1 knockdown blocked the induction of Npnt in hepatocytes and attenuated T lymphocyte migration
中文翻译:
BRG1介导肾细胞内肾上腺素激活,以促进ConA诱导的肝炎中T淋巴细胞浸润。
暴发性肝炎(FH)是急性肝衰竭的主要原因。伴刀豆球蛋白A(ConA)属于凝集素家族,经常在动物模型中用作促性腺激素的诱导剂。ConA诱导的FH的特征是肝脏中T淋巴细胞大量积累。已知许多化学吸引性物质可在急性肝炎期间促进T细胞归巢至肝脏。在这里,我们调查了婆罗门相关基因1(BRG1),染色质重塑蛋白,在FH中的参与。将BRG1-flox小鼠与Alb-Cre小鼠杂交,以产生肝细胞条件性BRG1敲除(LKO)小鼠。给小鼠腹膜注射单剂量的ConA以诱导FH。BRG1缺乏症减轻了ConA诱导的小鼠FH。一致地,与下调T细胞特异性细胞因子的野生型(WT)肝脏相比,LKO肝脏中的T淋巴细胞浸润较少。进一步的分析表明,BRG1缺乏抑制了对T细胞归巢至关重要的几种趋化因子的表达,其中包括肾粘连蛋白(Npnt)。BRG1敲低阻止了肝细胞中Npnt的诱导和T淋巴细胞迁移的减弱