Glia Maturation Factor-β Supports Liver Regeneration by Remodeling Actin Network to Enhance STAT3 Proliferative Signals.
Glia Maturation Factor-β Supports Liver Regeneration by Remodeling Actin Network to Enhance STAT3 Proliferative Signals.
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神经胶质成熟因子-β 通过重塑肌动蛋白网络增强 STAT3 增殖信号来支持肝脏再生
DOI：
10.1016/j.jcmgh.2022.07.016
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发表时间：
2022
影响因子：
7.2
通讯作者：
Wang, Yan
中科院分区：
文献类型：
--
作者：
Yin, Guo;Zeng, Weilan;Li, Rong;Zeng, Manman;Chen, Ronghua;Liu, Yaxue;Jiang, Ronglong;Wang, Yan
胶质细胞成熟因子β(GMFB)是肌动蛋白解聚因子同源家族的真正成员。最近，新的证据表明它在肝脏疾病中的作用，但关于它在肝脏中的作用的数据仍然有限。在急性肝损伤的小鼠模型上，评估了GMFB在肝脏组织学、对肝再生和肝细胞增殖的影响以及潜在的分子途径。GMFB在正常肝脏中广泛分布。在肝部分切除(PHX)后24小时内，其表达增加。成年Gmfb基因敲除小鼠和野生型小鼠在大体外观、体重、肝功能和组织学上相似。然而，与野生型对照相比，PHX后Gmfb基因敲除小鼠发生了更严重的肝损伤和脂肪变性，并延迟了肝脏再生；PHX后24小时肝脏转录组的主要变化是显著抑制了急性炎症途径；最高下调的基因集与白细胞介素6/Janus激酶/信号转导和转录激活因子3(STAT3)信号转导有关。另一种四氯化碳中毒的小鼠模型也重复了这些发现。此外，Gmfb基因敲除组和野生型Kupffer细胞数量相似，但一旦被刺激，Gmfb基因敲除Kupffer细胞产生的IL-6、肿瘤坏死因子和IL-1β较少。在IL6处理的肝细胞中，GMFB与细胞增殖和STAT3/Cyclin D1的激活呈正相关，但与STAT3没有直接的相互作用。在Gmfb基因敲除的肝细胞中，细胞骨架相关基因的表达发生了显著变化，出现了异常的肌动蛋白网络形态。在肝细胞模型中，肌动蛋白细丝的周转、STAT3的激活和代谢物的排泄都强烈依赖于肌动蛋白细丝组织的状态。GMFB通过促进Kupffer细胞的急性炎症反应和细胞内协调反应性肝细胞的增殖，在肝再生中发挥重要作用。
Glia maturation factor-β (GMFB) is a bona fide member of the actin depolymerizing factor homology family. Recently, emerging evidence suggested its implication in liver diseases, but data on its role in liver remain limited. Assessment of GMFB in liver histology, impact on liver regeneration and hepatocyte proliferation, and the underlying molecular pathways were conducted using mouse models with acute liver injury. GMFB is widely distributed in normal liver. Its expression increases within 24 hours after partial hepatectomy (PHx). Adult Gmfb knockout mice and wild-type littermates are similar in gross appearance, body weight, liver function, and histology. However, compared with wild-type control, Gmfb knockout mice post-PHx develop more serious liver damage and steatosis and have delayed liver regeneration; the dominant change in liver transcriptome at 24 hours after PHx is the significantly suppressed acute inflammation pathways; the top down-regulated gene sets relate to interleukin (IL)6/Janus kinase/signal transducer and activator of transcription 3 (STAT3) signaling. Another mouse model intoxicated with carbon tetrachloride replicated these findings. Furthermore, Gmfb knockout and wild-type groups have the similar numbers of Kupffer cells, but Gmfb knockout Kupffer cells once stimulated produce less IL6, tumor necrosis factor, and IL1β. In hepatocytes treated with IL6, GMFB associates positively with cell proliferation and STAT3/cyclin D1 activation, but without any direct interaction with STAT3. In Gmfb knockout hepatocytes, cytoskeleton-related gene expression was changed significantly, with an abnormal-appearing morphology of actin networks. In hepatocyte modeling, actin-filament turnover, STAT3 activation, and metabolite excretion show a strong reliance on the status of actin-filament organization. GMFB plays a significant role in liver regeneration by promoting acute inflammatory response in Kupffer cells and by intracellularly coordinating the responsive hepatocyte proliferation.
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影响因子：
64.8
作者：
Karin M;Clevers H
通讯作者：
Clevers H
影响因子：
5.1
作者：
Kitto LJ;Henderson NC
通讯作者：
Henderson NC
DOI：
10.1083/jcb.201501094
发表时间：
2015-06-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Haynes EM;Asokan SB;King SJ;Johnson HE;Haugh JM;Bear JE
通讯作者：
Bear JE
DOI：
10.1016/j.bbagen.2003.12.006
发表时间：
2004-02-24
影响因子：
3
作者：
Inagaki, M;Aoyama, M;Asai, K
通讯作者：
Asai, K
影响因子：
24.1
作者：
Ahmed, Yeni Ait;Fu, Yaojie;Gao, Bin
通讯作者：
Gao, Bin