First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
J Thromb Haemost. 2017 May;15(5):998-1008. doi: 10.1111/jth.13672. Epub 2017 Apr 9.
Essentials Regeneration role of C-type lectin receptor-2 (CLEC-2) after 70% hepatectomy (HPx) was investigated. Wild-type or CLEC-2 deleted from platelets of chimeric mice (flKO) underwent HPx. The liver/body weight ratio was significantly lower in the flKO than in the wild-type. CLEC-2 plays an essential role in liver regeneration after HPx.
Background and aim The aim of the present study was to investigate the role of C-type lectin receptor (CLEC)-2 in liver regeneration following partial liver resection in mice. Materials and methods Irradiated chimeric mice transplanted with fetal liver cells from wild-type (WT) mice, CLEC-2-deleted (KO) mice or mice with CLEC-2 deleted specifically from platelets (flKO) were generated. Mice underwent 70% partial hepatectomy (PH). Immunohistochemical staining was performed to investigate the expression of the endogenous ligand for CLEC-2, podoplanin. The accumulation of platelets in the liver was also quantified. The hepatic expression of the IL-6/gp130 and STAT3, Akt and ERK1/2 was also examined. Results The liver/body weight ratio and expression of all cell proliferation markers were significantly lower in the flKO group than in the WT group. The expression of phosphorylated (p) Akt and pERK1/2 was similar in the WT and flKO groups. On the other hand, the expression of pSTAT3 and IL-6 was significantly stronger in the WT group than in the flKO group. The expression of podoplanin was detected in the hepatic sinusoids of both groups. However, the extent to which platelets accumulated in hepatic sinusoids was significantly less in the flKO group than in the WT group. Conclusion CLEC-2 was involved in hepatic regeneration after liver resection and CLEC-2-related liver regeneration was attributed to the interaction between platelets and sinusoidal endothelial cells.
研究了 C 型凝集素受体-2（CLEC-2）在 70%肝切除（HPx）后的再生作用。接受 HPx 的嵌合小鼠（flKO）的血小板缺失野生型或 CLEC-2。与野生型相比，flKO 的肝/体重比明显较低。CLEC-2 在 HPx 后肝再生中起重要作用。
背景和目的本研究旨在探讨 C 型凝集素受体（CLEC）-2 在小鼠部分肝切除后肝再生中的作用。
材料和方法生成了辐照嵌合小鼠，这些小鼠移植了来自野生型（WT）小鼠、CLEC-2 缺失（KO）小鼠或血小板中 CLEC-2 特异性缺失（flKO）的胎儿肝细胞。小鼠接受 70%部分肝切除术（PH）。进行免疫组织化学染色以研究 CLEC-2 的内源性配体 podoplanin 的表达。还定量了血小板在肝脏中的积累。还检查了 IL-6/gp130 和 STAT3、Akt 和 ERK1/2 的肝表达。
结果 flKO 组的肝/体重比和所有细胞增殖标志物的表达均明显低于 WT 组。WT 和 flKO 组的磷酸化（p）Akt 和 pERK1/2 的表达相似。另一方面，WT 组的 pSTAT3 和 IL-6 的表达明显强于 flKO 组。两组肝窦中均检测到 podoplanin 的表达。然而，flKO 组血小板在肝窦中的积累程度明显低于 WT 组。
结论 CLEC-2 参与了肝切除后的肝再生，CLEC-2 相关的肝再生归因于血小板与肝窦内皮细胞之间的相互作用。
