Tmub1 (transmembrane and ubiquitin-like domain-containing 1) plays negative roles in rat hepatocyte proliferation, but its underlying molecular mechanisms in liver regeneration regulation have yet to be revealed. Here, we show that in vivo transfection of Tmub1 overexpression vectors impaired mouse liver regeneration after partial hepatectomy (PHx). Loss- and gain-of-function analyses in human hepatocyte Lo2 cells indicated that Tmub1 inhibits the phosphorylation of STAT3 and the activation of STAT3 signaling. Furthermore, the inhibitory effect of Tmub1 overexpression on hepatocyte proliferation can be reversed by the STAT3 activator OSM, while the promotive effect of Tmub1 knockdown can be abolished by the STAT3 inhibitor stattic. Coimmunoprecipitation assays revealed interaction between Tmub1 and STAT3. Finally, we present data from chromatin immunoprecipitation and luciferase reporter gene assays and report that STAT3 binds to and activates the promoter of Tmub1, suggesting a putative negative feedback loop between Tmub1 and STAT3 signaling. Taken together, the results of our study suggest that Tmub1 is an important negative regulator of hepatocyte proliferation in liver regeneration through STAT3 signaling. These findings provide a potential strategy for the management of liver regeneration.

Tmub1（跨膜和泛素样域包含1）在大鼠肝细胞增殖中起负作用，但其在肝脏再生调节中的潜在分子机制尚未揭示。在这里，我们显示Tmub1过表达载体的体内转染损害了部分肝切除术（PHx）后的小鼠肝脏再生。在人肝细胞Lo2细胞中的功能丧失和功能获得分析表明，Tmub1抑制STAT3的磷酸化和STAT3信号的激活。此外，STAT3激活剂OSM可逆转Tmub1过表达对肝细胞增殖的抑制作用，而STAT3抑制剂可消除Tmub1敲低的促进作用。免疫共沉淀测定揭示了Tmub1和STAT3之间的相互作用。最后，我们提供了来自染色质免疫沉淀和荧光素酶报告基因检测的数据，并报告STAT3结合并激活Tmub1的启动子，提示Tmub1和STAT3信号之间存在一个假定的负反馈回路。综上所述，我们的研究结果表明，Tmub1是肝细胞通过STAT3信号通路再生中肝细胞增殖的重要负调节剂。这些发现为肝再生的管理提供了潜在的策略。我们的研究结果表明，Tmub1是通过STAT3信号传导在肝再生中肝细胞增殖的重要负调节剂。这些发现为肝再生的管理提供了潜在的策略。我们的研究结果表明，Tmub1是通过STAT3信号传导在肝再生中肝细胞增殖的重要负调节剂。这些发现为肝再生的管理提供了潜在的策略。