Upregulation of necroptosis markers RIPK3/MLKL and their crosstalk with autophagy-related protein Beclin-1 in primary immune thrombocytopenia

Kamal, Amany M.; Nabih, Nermeen A.; Rakha, Nahed Moawad; Sanad, Eman F.

doi:10.1007/s10238-022-00839-8

Cited by 2 publications

(1 citation statement)

References 60 publications

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“…In COVID-19 patients, platelets undergo necroptosis, as suggested by pathway enrichment analysis of the platelet transcriptome and increased levels of pMLKL [51]. Platelet necroptosis may also play a critical role in primary immune thrombocytopenia (ITP), as the MLKL mRNA levels in ITP patients were inversely correlated with platelet count [52]. In SFTS patients, although the increase in platelet MLKL levels was not as great as the levels of pyroptosis and apoptosis biomarkers, their increase still indicated a role of necroptosis in thrombocytopenia.…”

Section: Discussionmentioning

confidence: 99%

RNA transcriptome analysis of platelets revealed altered platelet responses and the mechanism of thrombocytopenia in SFTS

Fang,

Zhang,

et al. 2023

Preprint

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Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne viral hemorrhagic fever disease caused by infection with Dabie bandavirus (SFTS virus, SFTSV). Thrombocytopenia is the primary clinical feature of SFTS and is significantly associated with disease severity. However, the pathological mechanism of thrombocytopenia in SFTS remains unclear. Methods Platelets purified from SFTS patients were subjected to RNA transcriptome analyses. Differentially expressed genes (DEGs) in the platelets of deceased and surviving patients were identified, and their functions and transcription levels were characterized. DEGs related to cell death were compared with the platelets of COVID-19 and dengue fever patients. The percentage of platelets positive for biomarkers of pyroptosis, apoptosis, necroptosis, autophagy, and ferroptosis was determined by flow cytometry. RNA transcriptome analyses were also performed with platelets purified from nonlethal SFTSV infection model mice. DEGs representing the functional changes in mouse platelets were characterized, and platelet death was also investigated. Functional platelet changes in SFTS patients and SFTSV-infected mice were compared to determine the different mechanisms underlying thrombocytopenia in humans and mice. Results Platelet transcriptome analyses revealed altered platelet functioning in SFTS patients and suggested an active platelet response in surviving patients but not in fatal patients. Enhanced neutrophil activation, interferon (IFN) signaling, and the virus life cycle were common platelet responses in SFTS. The increased histone methylation and impaired vesicle organization in platelets may be related to the fatal outcome, while the enhanced protein transport to membrane and RNA catabolic process may contribute to disease recovery. Moreover, SFTSV infection resulted in platelet loss via pyroptosis, apoptosis, necroptosis, and autophagy but not ferroptosis. Unlike platelets in SFTS patients, platelets in SFTSV-infected mice play a role mainly in regulating adaptive immunity, and platelet death in mice was not as severe as that in humans. Conclusions This study revealed altered platelet functioning in response to SFTSV infection and the mechanisms of thrombocytopenia in humans, which are different from those in mice infected with SFTSV. The results deepen our understanding of the pathogenesis of thrombocytopenia in SFTS and provides insights for subsequent studies on SFTS pathogenesis and the development of novel intervention strategies.

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Section: Discussionmentioning

confidence: 99%

RNA transcriptome analysis of platelets revealed altered platelet responses and the mechanism of thrombocytopenia in SFTS

Fang,

Zhang,

et al. 2023

Preprint

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Decreased gene expression of RIPK1 and RIPK3, necroptosis players, in calves with sepsis

DOGAN,

BAYKAN,

AKÇORA YILDIZ

2023

Veterinary Journal of Mehmet Akif Ersoy University

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Background With the increase in the world population, the need for livestock-based nutrition is also increasing. In addition, the livestock sector becomes more important as it contributes to the economy However, sepsis has high morbidity and mortality rate in newborn calves and can cause severe economic losses. Therefore, new biomarkers to distinguish sepsis from other diseases are urgently needed in veterinary medicine. In the present study, we investigated for the first time the gene expression levels of necroptosis members, including RIPK1 and RIPK3, and one of the NF-kB activators RIPK2, in calves with sepsis. Methods and results We examined the mRNA levels of RIPK1, RIPK3, and RIPK2 using qPCR in 10 healthy Holstein calves and 20 Holstein calves with sepsis due to suffering from enteritis infection between 1-20 days of age. The hematologic parameters, including leukocytes, erythrocytes, hemoglobin, hematocrit, and platelets, were evaluated in the calves included in this study. The results showed that calves with sepsis had prominently lower mRNA levels of RIPK1 and RIPK3 than those in healthy calves. Besides, RIPK2 mRNA expression was absent in healthy calves and calves with sepsis. Conclusions In veterinary medicine decreased RIPK1 and RIPK3 mRNA levels might be biomarkers to diagnose sepsis in calves.

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Upregulation of necroptosis markers RIPK3/MLKL and their crosstalk with autophagy-related protein Beclin-1 in primary immune thrombocytopenia

Cited by 2 publications

References 60 publications

RNA transcriptome analysis of platelets revealed altered platelet responses and the mechanism of thrombocytopenia in SFTS

RNA transcriptome analysis of platelets revealed altered platelet responses and the mechanism of thrombocytopenia in SFTS

Decreased gene expression of RIPK1 and RIPK3, necroptosis players, in calves with sepsis

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