Platelets Promote Liver Regeneration under Conditions of Kupffer Cell Depletion after Hepatectomy in Mice

Murata, Soichiro; Matsuo, Ryota; Ikeda, Osamu; Myronovych, Andriy; Watanabe, Motonobu; Hisakura, Katsuji; Nakano, Yoritaka; Hashimoto, Ikuka; Ohkohchi, Nobuhiro

doi:10.1007/s00268-008-9493-0

Cited by 56 publications

(74 citation statements)

References 54 publications

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“…The liver-regenerative effect has been shown by several in-vitro experiments and animal models [11,14,[17][18][19]. This has been confirmed by several animal studies [11,14,[20][21][22]. The results of this study confirm that low platelet counts are associated with increased postoperative morbidity and need of operative revision after partial liver resections in humans.…”

Section: Discussionsupporting

confidence: 77%

“…Platelets contain many growth factors as Platelet Derived Growth Factor (PDGF), Vascular Endothelial Growth Factor (VEGF), HGF, IGF, EGF and TGFb and some cytokines [17,19,30]. Due to those growths factors, platelets play a role in stimulation and acceleration of hepatocyte proliferation resulting in improved liver regeneration [11,18,20,31,32]. Mobilisation and increase of platelet numbers is mediated by thrombopoietin that is mainly produced in the liver.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Low Postoperative Platelet Count is Associated with Higher Morbidity after Liver Surgery for Colorectal Metastase

Riediger¹

2014

J Liver

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Low Postoperative Platelet Count is Associated with Higher Morbidity after Liver Surgery for Colorectal Metastase

Riediger¹

2014

J Liver

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“…Murata et al reported that platelets promote liver regeneration in the early period in a murine model [46]. Furthermore, Alkozai et al reported that a low platelet count immediately after partial hepatectomy was associated with delayed recovery of liver function [47].…”

Section: Discussionmentioning

confidence: 99%

Relationship of Hepatic Functional Parameters with Changes of Functional Liver Volume Using Technetium-99m Galactosyl Serum Albumin Scintigraphy in Patients Undergoing Preoperative Portal Vein Embolization: A Follow-Up Report

Nanashima¹,

Tobinaga²,

Abo³

et al. 2010

Journal of Surgical Research

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“…6 Conversely, following a partial liver resection in animals with a drug-induced thrombocytosis, liver regeneration was accelerated. 9,10 In a clinical study, we showed that a low platelet count is an independent predictor of delayed postoperative liver function recovery following a partial liver resection, suggesting that platelets stimulate liver regeneration also in humans. 11 The molecular mechanisms of platelet-mediated stimulation of liver regeneration are largely unexplored.…”

Section: Introductionmentioning

confidence: 95%

Horizontal RNA transfer mediates platelet-induced hepatocyte proliferation

Kirschbaum¹,

Karimian²,

Adelmeijer³

et al. 2015

Blood

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Key Points• Platelets stimulate proliferation of HepG2 cells, which requires uptake of platelets by the HepG2 cell.• Platelets stimulate HepG2 cell proliferation in part by transfer of RNA from the anucleate platelet to the nucleated HepG2 cell.Liver regeneration is stimulated by blood platelets, but the molecular mechanisms involved are largely unexplored. Although platelets are anucleate, they do contain coding or regulatory RNAs that can be functional within the platelet or, after transfer, in other cell types. Here, we show that platelets and platelet-like particles (PLPs) derived from the megakaryoblastic cell line MEG-01 stimulate proliferation of HepG2 cells. Platelets or PLPs were internalized within 1 hour by HepG2 cells and accumulated in the perinuclear region of the hepatocyte. Platelet internalization also occurred following a partial hepatectomy in mice. Annexin A5 blocked platelet internalization and HepG2 proliferation. We labeled total RNA of MEG-01 cells by incorporation of 5-ethynyluridine (EU) and added EU-labeled PLPs to HepG2 cells. PLP-derived RNA was detected in the cytoplasm of the HepG2 cell. We next generated PLPs containing green fluorescent protein (GFP)-tagged actin messenger RNA. PLPs did not synthesize GFP, but in coculture with HepG2 cells, significant GFP protein synthesis was demonstrated. RNA-degrading enzymes partly blocked the stimulating effect of platelets on hepatocyte proliferation. Thus, platelets stimulate hepatocyte proliferation via a mechanism that is dependent on platelet internalization by hepatocytes followed by functional transfer of RNA stored in the anucleate platelet. This mechanism may contribute to platelet-mediated liver regeneration. (Blood. 2015;126(6):798-806) IntroductionBlood platelets have essential roles in hemostasis and thrombosis, inflammation, host defense, and wound healing. [1][2][3][4] Emerging evidence from recent in vitro and in vivo studies suggests that platelets have a pivotal role in liver regeneration. [5][6][7][8] In experimental animal models in which platelets were depleted or functionally impaired, liver regeneration after a partial liver resection was substantially delayed. 6 Conversely, following a partial liver resection in animals with a drug-induced thrombocytosis, liver regeneration was accelerated. 9,10 In a clinical study, we showed that a low platelet count is an independent predictor of delayed postoperative liver function recovery following a partial liver resection, suggesting that platelets stimulate liver regeneration also in humans. 11The molecular mechanisms of platelet-mediated stimulation of liver regeneration are largely unexplored. Platelets contain 2 distinct types of storage organelles: a granules and dense granules. The a granules contain, among many proteins, a number of growth factors that have an established role in liver regeneration (platelet-derived growth factor [PDGF], hepatocyte growth factor [HGF], insulin-like growth factor [IGF], and vascular endothelial growth factor [VEGF]). 8,12 In addition...

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Platelets Promote Liver Regeneration under Conditions of Kupffer Cell Depletion after Hepatectomy in Mice

Cited by 56 publications

References 54 publications

Low Postoperative Platelet Count is Associated with Higher Morbidity after Liver Surgery for Colorectal Metastase

Low Postoperative Platelet Count is Associated with Higher Morbidity after Liver Surgery for Colorectal Metastase

Relationship of Hepatic Functional Parameters with Changes of Functional Liver Volume Using Technetium-99m Galactosyl Serum Albumin Scintigraphy in Patients Undergoing Preoperative Portal Vein Embolization: A Follow-Up Report

Horizontal RNA transfer mediates platelet-induced hepatocyte proliferation

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