LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy.
LPS/Bcl3/YAP1 signaling promotes Sox9(+)HNF4α(+) hepatocyte-mediated liver regeneration after hepatectomy.
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LPS/BCL3/YAP1信号传导促进Sox9（+）Hnf4α（+）肝细胞介导的肝切除术后的肝脏再生。
DOI：
10.1038/s41419-022-04715-x
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发表时间：
2022-03-28
影响因子：
9
通讯作者：
Wei L
中科院分区：
文献类型：
--
作者：
Shao C;Jing Y;Zhao S;Yang X;Hu Y;Meng Y;Huang Y;Ye F;Gao L;Liu W;Sheng D;Li R;Zhang X;Wei L
近年来的研究表明，Sox9+HNF4α+肝细胞参与了慢性肝损伤后的肝再生过程，但对Sox9+HNF4α+肝细胞的起源及其调控机制尚不清楚。采用嵌合谱系追踪、免疫荧光和免疫组织化学相结合的方法，我们证明了Sox 9 + HNF 4 α+肝细胞（由成熟肝细胞转化而成）在部分肝切除术（PHx）后的初始阶段起着重要作用。此外，敲低Sox 9的表达抑制肝细胞增殖并阻断丧失的肝组织的恢复。体外和体内试验表明，Bcl 3，由LPS激活，促进肝细胞转化和肝再生。在机制上，Bcl 3与YAP 1形成复合物并使YAP 1去泛素化，并进一步诱导YAP 1易位到细胞核中，导致Sox 9上调和成熟肝细胞转化。我们证明Bcl 3促进Sox 9 + HNF 4 α+肝细胞参与肝再生，因此可能是促进肝损伤后再生的潜在靶点。
Recent reports have demonstrated that Sox9+HNF4α+ hepatocytes are involved in liver regeneration after chronic liver injury; however, little is known about the origin of Sox9+HNF4α+ hepatocytes and the regulatory mechanism. Employing a combination of chimeric lineage tracing, immunofluorescence, and immunohistochemistry, we demonstrate that Sox9+HNF4α+ hepatocytes, generated by transition from mature hepatocytes, play an important role in the initial phase after partial hepatectomy (PHx). Additionally, knocking down the expression of Sox9 suppresses hepatocyte proliferation and blocks the recovery of lost hepatic tissue. In vitro and in vivo assays demonstrated that Bcl3, activated by LPS, promotes hepatocyte conversion and liver regeneration. Mechanistically, Bcl3 forms a complex with and deubiquitinates YAP1 and further induces YAP1 to translocate into the nucleus, resulting in Sox9 upregulation and mature hepatocyte conversion. We demonstrate that Bcl3 promotes Sox9+HNF4α+ hepatocytes to participate in liver regeneration, and might therefore be a potential target for enhancing regeneration after liver injury.
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影响因子：
13.5
作者：
Fausto, N;Campbell, JS;Riehle, KJ
通讯作者：
Riehle, KJ
影响因子：
--
作者：
Abu Rmilah, Anan;Zhou, Wei;Nyberg, Scott L.
通讯作者：
Nyberg, Scott L.
谱系追踪揭示了 SOX9 肝细胞在肝脏再生过程中的双能性
影响因子：
5.9
作者：
Han, Ximeng;Wang, Yue;Zhou, Bin
通讯作者：
Zhou, Bin
影响因子：
--
作者：
Feng, X;Jiang, Y;Yen, PM
通讯作者：
Yen, PM
影响因子：
9.3
作者：
Jing YY;Han ZP;Sun K;Zhang SS;Hou J;Liu Y;Li R;Gao L;Zhao X;Zhao QD;Wu MC;Wei LX
通讯作者：
Wei LX