Interplay of hepatic and myeloid signal transducer and activator of transcription 3 in facilitating liver regeneration via tempering innate immunity.
Interplay of hepatic and myeloid signal transducer and activator of transcription 3 in facilitating liver regeneration via tempering innate immunity.
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DOI：
10.1002/hep.23430
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发表时间：
2010-04
期刊：
影响因子：
13.5
通讯作者：
Gao, Bin
中科院分区：
文献类型：
--
作者：
Wang, Hua;Park, Ogyi;Lafdil, Fouad;Shen, Kezhen;Horiguchi, Norio;Yin, Shi;Fu, Xin-Yuan;Kunos, George;Gao, Bin
2/3部分肝切除术触发的肝脏再生伴随着肝脏内毒素水平的升高，这有助于再生过程，但肝脏炎症和细胞凋亡仍然受到矛盾的限制。在这里，我们发现 STAT3（一种重要的抗炎信号）在部分肝切除术后在骨髓细胞中被激活，并且其条件性缺失导致炎症反应增强。令人惊讶的是，这伴随着肝脏 STAT3 激活增加的再生反应的改善而不是受损，这可能有助于增强肝脏再生。事实上，肝细胞和骨髓细胞中 STAT3 的条件性缺失会导致 STAT1 激活升高和肝细胞凋亡，并导致部分肝切除术后存活率急剧下降，而 STAT1 的额外整体缺失可以防止这些影响。结论：骨髓和肝脏 STAT3 信号传导的相互作用对于通过缓和 STAT1 信号传导介导的强烈先天炎症反应来预防肝再生过程中的肝衰竭至关重要。
Liver regeneration triggered by 2/3 partial hepatectomy is accompanied by elevated hepatic levels of endotoxin, which contributes to the regenerative process, but liver inflammation and apoptosis remain paradoxically limited. Here we show that STAT3, an important anti-inflammatory signal, is activated in myeloid cells after partial hepatectomy and its conditional deletion results in an enhanced inflammatory response. Surprisingly, this is accompanied by an improved rather than impaired regenerative response with increased hepatic STAT3 activation, which may contribute to the enhanced liver regeneration. Indeed, conditional deletion of STAT3 in both hepatocytes and myeloid cells results in elevated activation of STAT1 and apoptosis of hepatocytes, and a dramatic reduction in survival after partial hepatectomy, whereas additional global deletion of STAT1 protects against these effects. Conclusions: An interplay of myeloid and hepatic STAT3 signaling is essential to prevent liver failure during liver regeneration through tempering a strong innate inflammatory response mediated by STAT1 signaling.
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影响因子：
8
作者：
Lin, L.;Amin, R.;Gallicano, G. I.;Glasgow, E.;Jogunoori, W.;Jessup, J. M.;Zasloff, M.;Marshall, J. L.;Shetty, K.;Johnson, L.;Mishra, L.;He, A. R.
通讯作者：
He, A. R.
影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
29.4
作者：
Duong, FHT;Filipowicz, M;Heim, MH
通讯作者：
Heim, MH
影响因子：
32.4
作者：
Takeda, K;Clausen, BE;Akira, S
通讯作者：
Akira, S
影响因子：
4.8
作者：
Li, W;Liang, XP;Taub, R
通讯作者：
Taub, R