αMSH inhibits adipose inflammation via reducing FoxOs transcription and blocking Akt/JNK pathway in mice.
αMSH inhibits adipose inflammation via reducing FoxOs transcription and blocking Akt/JNK pathway in mice.
复制标题
αMSH通过减少FOXOS转录并阻止小鼠的Akt/JNK途径来抑制脂肪炎症。
DOI：
10.18632/oncotarget.17465
复制
发表时间：
2017-07-18
期刊：
影响因子：
--
通讯作者：
Sun C
中科院分区：
文献类型：
--
作者：
Liu G;Li M;Saeed M;Xu Y;Ren Q;Sun C
α 黑素细胞刺激激素 (αMSH) 可减轻多个组织的炎症，而叉头盒蛋白 O (FoxO) 则可刺激炎症级联反应。然而，αMSH 和 FoxOs 在脂肪炎症中的关系仍不清楚。在本研究中，我们使用LPS诱导的炎症模型，试图解释αMSH在炎症中的功能以及与FoxOs的相互作用。结果表明，炎症状态下，αMSH的分泌及其受体MC5R的表达大大减少，而FoxOs的表达却升高。用αMSH治疗后，LPS诱导的脂肪炎症和FoxOs表达显着减少。相反，当 Foxo1、Foxo3a 或 Foxo4 在 αMSH 治疗的炎症小鼠模型中过表达时，发现 αMSH 的所有抗炎作用都消失了。我们进一步研究了 αMSH 发挥抗炎作用的机制以及 FoxOs 如何逆转 αMSH 的功能。 Foxo4被发现是αMSH抑制炎症中MC5R转录的负调节因子。此外，通过观察 αMSH 治疗途径特异性抑制剂增强的抗炎作用，发现 αMSH 在调节 Akt 和 JNK 信号途径中发挥负面作用。我们的研究结果表明，αMSH 通过下调 Akt/JNK 信号通路并与 FoxOs 负相互作用，在预防脂肪炎症和炎症性疾病中发挥着关键作用，这使得 αMSH 成为肥胖症脂肪抗炎过程中的新候选因子。
Alpha melanocyte stimulating hormone (αMSH) abates inflammation in multiple tissues, while Forkhead box proteins O (FoxOs) stimulate inflammatory cascade. However, the relationship between αMSH and FoxOs in adipose inflammation remains unclear. In this study, we used LPS-induced inflammation model, attempted to interpret the function of αMSH in inflammation and the interactions with FoxOs. Results indicated that upon inflammatory situation, the secretion of αMSH and the expression of its receptor MC5R were greatly decreased, but FoxOs expressions were elevated. After the treatment with αMSH, LPS-induced adipose inflammation together with FoxOs expressions was significantly reduced. Conversely, when Foxo1, Foxo3a or Foxo4 overexpressed in αMSH treated inflammatory mouse model, all the anti-inflammatory impacts of αMSH were found disappeared. We further studied the mechanisms by which αMSH exerts its anti-inflammatory impacts and how FoxOs reverse αMSH's function. Foxo4 was found as a negative regulator for MC5R transcription in αMSH inhibited inflammation. Moreover, a negative role was found of αMSH in regulating both Akt and JNK signal pathways by observing the enhanced the anti-inflammatory impacts of pathway-specific inhibitors with αMSH treatment. Our findings demonstrate αMSH plays a key role in the prevention of adipose inflammation and inflammatory diseases by down-regulating Akt/JNK signal pathway and negatively interacting with FoxOs, which brings up αMSH as a novel candidate factor in the adipose anti-inflammation process in obesity.
登录
查看更多内容
DOI：
10.1165/rcmb.2009-0420oc
发表时间：
2011-05-01
影响因子：
6.4
作者：
Lee, Sang-Nam;Ryu, Ji-Hwan;Yoon, Joo-Heon
通讯作者：
Yoon, Joo-Heon
巨噬细胞的局部扩散有助于与肥胖相关的脂肪组织炎症。
影响因子：
29
作者：
Amano SU;Cohen JL;Vangala P;Tencerova M;Nicoloro SM;Yawe JC;Shen Y;Czech MP;Aouadi M
通讯作者：
Aouadi M
α-MSH 和 Foxc2 通过小鼠脂肪组织中的 C/EBP β 负转录促进脂肪酸氧化
影响因子：
4.6
作者：
Gan L;Liu Z;Chen Y;Dan Luo;Feng F;Liu G;Sun C
通讯作者：
Sun C
影响因子：
7.7
作者：
Kawano Y;Nakae J;Watanabe N;Fujisaka S;Iskandar K;Sekioka R;Hayashi Y;Tobe K;Kasuga M;Noda T;Yoshimura A;Onodera M;Itoh H
通讯作者：
Itoh H
影响因子：
82.9
作者：
Jonsson, H;Allen, P;Peng, SL
通讯作者：
Peng, SL