The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling

Grozovsky, Renata; Begonja, Antonija Jurak; Liu, Kaifeng; Visner, Gary; Hartwig, John H.; Falet, Hervé; Hoffmeister, Karin M.

doi:10.1038/nm.3770

Cited by 277 publications

(316 citation statements)

References 51 publications

(64 reference statements)

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“…The production of platelets is highly regulated, because this is important to prevent serious bleeding when platelet counts are low, as well as to prevent vascular occlusion and organ damage when platelet counts are increased. Recently, it was elegantly shown that platelet production can be regulated by binding of desialylated platelets to the hepatic Ashwell-Morell receptor, which induces expression of TPO in the liver via JAK2-STAT3 signaling (133).…”

Section: Infections and Thrombocytopeniamentioning

confidence: 99%

Nouvelle Cuisine: Platelets Served with Inflammation

Kapur

Zufferey

Boilard

et al. 2015

The Journal of Immunology

177

191

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Platelets are small cellular fragments with the primary physiological role of maintaining hemostasis. In addition to this well-described classical function, it is becoming increasingly clear that platelets have an intimate connection with infection and inflammation. This stems from several platelet characteristics, including their ability to bind infectious agents and secrete many immunomodulatory cytokines and chemokines, as well as their expression of receptors for various immune effector and regulatory functions, such as TLRs, which allow them to sense pathogen-associated molecular patterns. Furthermore, platelets contain RNA that can be nascently translated under different environmental stresses, and they are able to release membrane microparticles that can transport inflammatory cargo to inflammatory cells. Interestingly, acute infections can also result in platelet breakdown and thrombocytopenia. This report highlights these relatively new aspects of platelets and, thus, their nonhemostatic nature in an inflammatory setting.

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Section: Infections and Thrombocytopeniamentioning

confidence: 99%

Nouvelle Cuisine: Platelets Served with Inflammation

Kapur

Zufferey

Boilard

et al. 2015

The Journal of Immunology

177

191

View full text Add to dashboard Cite

show abstract

“…Platelets desialylate as they circulate, thereby becoming the primary ligand for the AMR, 10 and this interaction regulates hepatocyte thrombopoietin production. 11 Desialylation also occurs when platelets are activated by several physiological stimuli, and AMR clearance may be relevant in attenuating the coagulopathy of sepsis. [12][13][14] Our results support the indications of international ITP guidelines, 15 which suggest that both PSSs and glycoprotein-specific antibody testing are not mandatory in ITP workup or management.…”

mentioning

confidence: 99%

Clinical relevance of antiplatelet antibodies and the hepatic clearance of platelets in patients with immune thrombocytopenia

Cantoni

Carpenedo

Nichelatti³

et al. 2016

Blood

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“…Compared with platelet transfusion, the degree of the improvement in the liver function was small, although adverse events did not occur. A recent report stated that the aging of platelets controls the production of TPO (Grozovsky et al 2015); thus, the aging and activation of platelets are involved in liver regeneration. During this clinical trial, no cancerous lesions were observed, which may ensure the safety of EP concerning cancer in patients with hepatitis and LC.…”

Section: Discussionmentioning

confidence: 99%

Stable Liver Function during Long-Term Administration of Eltrombopag, a Thrombopoietin Receptor Agonist, in Patients with Chronic Liver Disease

Kurokawa

Murata

Ohkohchi

2016

Tohoku J. Exp. Med.

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Liver cirrhosis is the end stage of chronic liver disease, but no definitive pharmacological treatment is currently available. It has been reported that thrombopoietin (TPO) promotes liver regeneration and improves liver cirrhosis by increasing platelet count. We have shown the direct effect of platelet transfusion on the improvement of liver function in patients with chronic liver disease. However, platelet transfusion often causes adverse events, such as platelet transfusion refractoriness and pruritus. Therefore, we conducted an exploratory clinical trial and administered eltrombopag, an orally bioavailable, small-molecule, non-peptide TPO receptor agonist that has been approved for the treatment of chronic idiopathic thrombocytopenic purpura. The study included five male patients, aged from 49 to 75 years (57.6 ± 10.4 years), with both chronic liver disease and hepatitis C virus infection, who presented with thrombocytopenia but without cancer. Eltrombopag, ranged from 6.25 to 50 mg/day (18.75 ± 18.22 mg/day), was administrated to the five patients during six months. All of the patients maintained platelet counts between 10 and 15 × 10 10 /L during the study. The indicators of liver function in patients were stable throughout the clinical trial, although we had predicted the same degree of the improvement of liver function, compared to platelet transfusion. Importantly, the liver volumes were also stable, and no cancerous lesions were observed. These results indicate the safety of long-term eltrombopag administration for patients with chronic liver disease and hepatitis C virus infection.

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The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling

Cited by 277 publications

References 51 publications

Nouvelle Cuisine: Platelets Served with Inflammation

Nouvelle Cuisine: Platelets Served with Inflammation

Clinical relevance of antiplatelet antibodies and the hepatic clearance of platelets in patients with immune thrombocytopenia

Stable Liver Function during Long-Term Administration of Eltrombopag, a Thrombopoietin Receptor Agonist, in Patients with Chronic Liver Disease

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