SOCS2 Suppresses Inflammation and Apoptosis during NASH Progression through Limiting NF-κB Activation in Macrophages.
SOCS2 Suppresses Inflammation and Apoptosis during NASH Progression through Limiting NF-κB Activation in Macrophages.
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DOI：
10.7150/ijbs.63889
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发表时间：
2021
影响因子：
9.2
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Li S;Han S;Jin K;Yu T;Chen H;Zhou X;Tan Z;Zhang G
背景：炎症和细胞凋亡在非酒精性脂肪性肝炎（NASH）的进展中起着至关重要的作用。细胞因子信号传导抑制因子2 （Suppressor of cytokine signaling, SOCS2）是细胞因子信号传导的典型负调控因子之一，近年来被描述为抗炎介质。然而，在NASH进展过程中，SOCS2在巨噬细胞中的作用以及SOCS2与炎症、细胞凋亡和NASH之间的关系在很大程度上是未知的。在此，我们旨在研究SOCS2在NASH进展中的功能。方法：检测无脂肪变性、单纯性脂肪变性和NASH患者巨噬细胞中SOCS2的表达，以证实SOCS2与NASH之间的关系。利用游离脂肪酸在稳定过表达或低表达SOCS2的RAW 264.7细胞系中建立应激环境。体外和体内实验也研究了SOCS2在NASH进展中的分子功能。研究结果：我们的人类样本表明，在NASH进展过程中，巨噬细胞中的SOCS2减少，并与NASH水平呈负相关。同时，体外实验表明，巨噬细胞中SOCS2过表达通过抑制NF-κB信号通路抑制炎症和凋亡，而巨噬细胞中SOCS2敲低导致NF-κB活化增加，可被1-吡罗烷二硫代氨基甲酸铵（PDTC）阻断。此外，巨噬细胞中的SOCS2还通过限制炎症小体的激活来抑制炎症。与此一致，我们的BMT模型也证实了NASH期间巨噬细胞中SOCS2的功能。解释：我们的数据强烈表明，在NASH中，SOCS2通过NF-κB和炎性小体信号通路在巨噬细胞中抑制炎症和细胞凋亡。需要进一步的研究来探索SOCS2对这种常见肝脏疾病的潜在预防和治疗策略。
Background: Inflammation and apoptosis play a crucial role in the progression of nonalcoholic steatohepatitis (NASH). Suppressor of cytokine signaling 2 (SOCS2) is one of classic negative regulators of cytokine signaling, which has recently been described as anti-inflammatory mediators. However, the role of SOCS2 in macrophages during NASH progression and the relationship among SOCS2, inflammation, apoptosis and NASH is largely unknown. Herein, we aimed to study the function of SOCS2 in NASH progression. Methods: We detected SOCS2 expression in macrophages in human subjects without steatosis, with simple steatosis and with NASH to confirm the relationship between SOCS2 and NASH. Free fatty acids was used to establish stress environment in RAW 264.7 cell lines stably overexpressing or knockdown SOCS2. In vitro and vivo assays also performed to study the molecular function of SOCS2 in NASH progression. Findings: Our human samples illustrated that SOCS2 was decreased in macrophages during NASH progression and was negatively correlated to NASH level. Meanwhile, In vitro assays showed SOCS2 overexpression in macrophages suppressed inflammation and apoptosis via inhibiting NF-κB signaling pathway, while SOCS2 knock-down in macrophages caused an increased activation of NF-κB, which could be blocked by ammonium 1-pyrrolidinedithiocarbamate (PDTC). In addition, SOCS2 in macrophages also suppressed inflammation via limiting the activation of inflammasomes. Consistent with these, our BMT model also confirmed the SOCS2 function in macrophages during NASH. Interpretation: Our data strongly indicate that SOCS2 plays a role in inhibiting inflammation and apoptosis via NF-κB and inflammasome signaling pathway in macrophages during NASH. Further studies are required to explore the potential preventive and therapeutic strategies of SOCS2 for this common liver disease.
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影响因子：
82.9
作者：
Friedman SL;Neuschwander-Tetri BA;Rinella M;Sanyal AJ
通讯作者：
Sanyal AJ
影响因子：
5.6
作者：
Nassir F;Ibdah JA
通讯作者：
Ibdah JA
影响因子：
4.8
作者：
Zadjali, Fahad;Santana-Farre, Ruyman;Flores-Morales, Amilcar
通讯作者：
Flores-Morales, Amilcar
人类脂肪肝病：旧问题和新见解。
DOI：
10.1126/science.1204265
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Cohen JC;Horton JD;Hobbs HH
通讯作者：
Hobbs HH
影响因子：
50.3
作者：
Haybaeck J;Zeller N;Wolf MJ;Weber A;Wagner U;Kurrer MO;Bremer J;Iezzi G;Graf R;Clavien PA;Thimme R;Blum H;Nedospasov SA;Zatloukal K;Ramzan M;Ciesek S;Pietschmann T;Marche PN;Karin M;Kopf M;Browning JL;Aguzzi A;Heikenwalder M
通讯作者：
Heikenwalder M