Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer

Malehmir, Mohsen; Pfister, Dominik; Gallage, Suchira; Szydlowska, Marta; Inverso, Donato; Kotsiliti, Eleni; Leone, Valentina; Peiseler, Moritz; Surewaard, Bas G. J.; Rath, Dominik; Ali, Adnan; Wolf, Monika; Drescher, Hannah K.; Healy, Marc E.; Dauch, Daniel; Kroy, Daniela C.; Krenkel, Oliver; Kohlhepp, Marlene; Engleitner, Thomas; Olkus, Alexander; Sijmonsma, Tjeerd P.; Volz, Joachim; Deppermann, Carsten; Stegner, David; Helbling, Patrick M.; Nombela‐Arrieta, César; Rafiei, Anahita; Hinterleitner, Martina; Rall, Marcel; Baku, Florian; Borst, Oliver; Wilson, Caroline; Leslie, Jack; O’Connor, Tracy; Weston, Chris J.; Adams, David H.; Sheriff, Lozan; Teijeiro, Ana; Prinz, Marco; Bogeska, Ruzhica; Anstee, Natasha S.; Bongers, Malte; Notohamiprodjo, Mike; Geisler, Tobias; Withers, Dominic J.; Ware, Jerry; Mann, Derek A.; Augustin, Hellmut G.; Vegiopoulos, Alexandros; Milsom, Michael D.; Rose, Adam J.; Lalor, Patricia F.; Llovet, Josep M.; Pinyol, Roser; Tacke, Frank; Rad, Roland; Matter, Matthias S.; Djouder, Nabil; Kubes, Paul; Knolle, Percy A.; Unger, Kristian; Zender, Lars; Nieswandt, Bernhard; Gawaz, Meinrad; Weber, Achim; Heikenwälder, Mathias

doi:10.1038/s41591-019-0379-5

Cited by 297 publications

(329 citation statements)

References 83 publications

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“…81 Recent data from our laboratories indicated an increase of infiltrating platelets in hepatic tissue of pre-clinical models of diet-induced NASH and of NASH-diagnosed patients. 82 Interestingly, this increase was not observed in livers displaying simple steatosis. However, genetic thrombocytopenia or pharmacological inhibition of platelet activation (aspirin/clopidrogel) not only reduced NAFLD activity score and inflammatory infiltrate but also turned out to improve steatosis, possibly by ameliorating mitochondrial functionality and lipid catabolism.…”

Section: Platelets In Alcohol-related and Non-alcoholic Steatohepatitismentioning

confidence: 93%

“…70 Similarly, as described in detail earlier, anti-platelet therapy prevented NASHinduced HCC mainly through modulation of the immune response. 82 However, platelet cargo has been shown to contain mediators and growth factors that can directly promote growth and invasion of HCC cell lines. 95 Increased levels of serotonin, stored in platelet granules and critical for liver regeneration, were detected in association with early disease recurrence in patients undergoing surgical resection for liver tumours.…”

Section: Platelets In Liver Cancer and Metastasismentioning

confidence: 99%

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Platelets in chronic liver disease, from bench to bedside

et al. 2019

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In the last decade, numerous studies revealed physiologic and pathophysiologic roles of platelets beyond haemostasis, a process to prevent and stop bleeding. These include the activation of the immune system and the promotion of inflammation, infection and cancer. Hence, the emerging view on the role of platelets has shiftedplatelets are now seen as alert "sentinels" of the immune compartment, rather than passive bystanders. Herein, we review well-established and newly discovered features of platelets that define their natural role in maintaining blood haemostasis, but also their functional relationship with other cells of the immune system. We focus on recent studies underlining functional involvement of platelets in chronic liver diseases and cancer, as well as the effects of anti-platelet therapy in these contexts. Finally, we illustrate the potential of platelets as possible diagnostic and therapeutic tools in liver disease based on recently developed methodologies.

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Section: Platelets In Alcohol-related and Non-alcoholic Steatohepatitismentioning

confidence: 93%

Section: Platelets In Liver Cancer and Metastasismentioning

confidence: 99%

Platelets in chronic liver disease, from bench to bedside

et al. 2019

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“…Antiplatelet therapy (aspirin/clopidogrel, ticagrelor) but not non-steroidal anti-inflammatory drug treatment with sulindac also prevented NASH and subsequent development of hepatocellular carcinoma in a murine hIL4r-alpha-/GP1balpha transgenic mouse model of NASH. 126 In addition, intra-vital microscopy also showed that antiplatelet therapy reduced intrahepatic platelet accumulation and the frequency of plateletimmune cell interaction, thereby limiting hepatic immune cell trafficking. Taken together, these experimental results suggest that blocking platelet activation might ameliorate NASH and subsequently decrease the risk of developing hepatocellular carcinoma.…”

Section: Platelet Activation As a Mediator Of The Link Between Nafld mentioning

confidence: 99%

NAFLD as a driver of chronic kidney disease

Byrne

Targher

2020

Journal of Hepatology

318

263

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Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are worldwide public health problems, affecting up to 25-30% (NAFLD), and up to 10-15% (CKD) of the general population. Recently, it has also been established that there is a strong association between NAFLD and CKD, regardless of the presence of potential confounding diseases such as obesity, hypertension and type 2 diabetes. Since NAFLD and CKD are both common diseases that often occur alongside other metabolic conditions, such as type 2 diabetes or metabolic syndrome, elucidating the relative impact of NAFLD on the risk of incident CKD presents a substantial challenge for investigators working in this research field. A growing body of epidemiological evidence suggests that NAFLD is an independent risk factor for CKD and recent evidence also suggests that associated factors such as metabolic syndrome, dysbiosis, unhealthy diets, platelet activation and processes associated with ageing could also contribute mechanisms linking NAFLD and CKD. This narrative review provides an overview of the literature on: a) the evidence for an association and causal link between NAFLD and CKD and b) the underlying mechanisms by which NAFLD (and factors strongly linked with NAFLD) may increase the risk of developing CKD.

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“…By releasing their α-granula contents, platelets might significantly contribute to the chronic intrahepatic inflammation. In agreement with this hypothesis, antiplatelet therapy was shown to prevent transformation of NASH into HCC and to partially revert NASH in a mouse model [8].…”

Section: Workhop On Infection and Cancermentioning

confidence: 52%

Report of the 23rd Meeting on Signal Transduction 2019—Trends in Cancer and Infection

Schirmer

Giehl

Kubatzky

2020

IJMS

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The annual meeting "Signal Transduction-Receptors, Mediators and Genes" of the Signal Transduction Society (STS) is an interdisciplinary conference open to all scientists sharing the common interest in elucidating the signalling pathways underlying the physiological or pathological processes in health and disease of humans, animals, plants, fungi, prokaryotes and protists. The 23rd meeting on signal transduction was held from 4-6 November 2019 in Weimar, Germany, and focused on "Trends in Cancer and Infection". As usual, keynote presentations by invited scientists introduced the respective workshops and were followed by speakers chosen from the submitted abstracts. Ample time had been reserved for discussion of the presented data during the workshops. In this report, we provide a concise summary of the various workshops and further aspects of the scientific program.

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Platelet GPIbα is a mediator and potential interventional target for NASH and subsequent liver cancer

Cited by 297 publications

References 83 publications

Platelets in chronic liver disease, from bench to bedside

Platelets in chronic liver disease, from bench to bedside

NAFLD as a driver of chronic kidney disease

Report of the 23rd Meeting on Signal Transduction 2019—Trends in Cancer and Infection

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