The platelet‐activating receptor C‐type lectin receptor‐2 plays an essential role in liver regeneration after partial hepatectomy in mice. (9th April 2017)

• Record Type: Journal Article
• Authors: Kono, H.; Fujii, H.; Suzuki‐Inoue, K.; Inoue, O.; Furuya, S.; Hirayama, K.; Akazawa, Y.; Nakata, Y.; Sun, C.; Tsukiji, N.; Shirai, T.; Ozaki, Y.
• Is Part Of: Journal of thrombosis and haemostasis. Volume 15:Number 5(2017)
• Page Start: 998
• Page End: 1008
• Publication Date: 2017-04-09
• Subjects: hepatectomy -- knockout mouse -- liver regeneration -- platelet -- serotonin; Thrombosis -- Periodicals; Hemostasis -- Periodicals; Blood coagulation disorders -- Periodicals; 616.1
• DOI: 10.1111/jth.13672
• Languages: English
• ISSNs: 1538-7933

Abstract

Abstract : 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. Summary: 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.