Autophagic regulation of platelet biology

Luo, Xuling; Jiang, Jinyong; Huang, Zhen; Chen, Linxi

doi:10.1002/jcp.28243

Cited by 12 publications

(5 citation statements)

References 56 publications

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“… 18 , 19 In recent years, it has been discovered that platelets can degrade damaged organelles through autophagy mechanisms to maintain intracellular homeostasis, which is similar to nucleated cells. 20 – 22 In 2014, Feng and colleagues first systematically elucidated the constitutive expression of the autophagy mechanism in human platelets, demonstrating its necessity to maintain the primary function. 7 Additionally, human platelets express components of the ULK1 complex, BECN1-PIK3C3 complex, and autophagosomes, confirming the existence of complete autophagic flux.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia

Yang,

Li,

et al. 2024

J Clin Transl Hepatol

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Background and Aims The role of platelet autophagy in cirrhotic thrombocytopenia (CTP) remains unclear. This study aimed to investigate the impact of platelet autophagy in CTP and elucidate the regulatory mechanism of hydrogen sulfide (H 2 S) on platelet autophagy. Methods Platelets from 56 cirrhotic patients and 56 healthy individuals were isolated for in vitro analyses. Autophagy markers (ATG7, BECN1, LC3, and SQSTM1) were quantified using enzyme-linked immunosorbent assay, while autophagosomes were visualized through electron microscopy. Western blotting was used to assess the autophagy-related proteins and the PDGFR/PI3K/Akt/mTOR pathway following treatment with NaHS (an H 2 S donor), hydroxocobalamin (an H 2 S scavenger), or AG 1295 (a selective PDGFR-α inhibitor). A carbon tetrachloride-induced cirrhotic BALB/c mouse model was established. Cirrhotic mice with thrombocytopenia were randomly treated with normal saline, NaHS, or hydroxocobalamin for 15 days. Changes in platelet count and aggregation rate were observed every three days. Results Cirrhotic patients with thrombocytopenia exhibited significantly decreased platelet autophagy markers and endogenous H 2 S levels, alongside increased platelet aggregation, compared to healthy controls. In vitro, NaHS treatment of platelets from severe CTP patients elevated LC3-II levels, reduced SQSTM1 levels, and decreased platelet aggregation in a dose-dependent manner. H 2 S treatment inhibited PDGFR, PI3K, Akt, and mTOR phosphorylation. In vivo , NaHS significantly increased LC3-II and decreased SQSTM1 expressions in platelets of cirrhotic mice, reducing platelet aggregation without affecting the platelet count. Conclusions Diminished platelet autophagy potentially contributes to thrombocytopenia in cirrhotic patients. H 2 S modulates platelet autophagy and functions possibly via the PDGFR-α/PI3K/Akt/mTOR signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia

Yang,

Li,

et al. 2024

J Clin Transl Hepatol

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“…In this study, increased levels of LC3B were observed, which suggested the occurrence of autophagy in the platelets of SFTS patients. Complete autophagic ux, from the formation of autophagosomes to autophagic degradation, is important for the number, size, and activation of platelets and could be a potential therapeutic target for hemorrhagic and thrombosis diseases [55]. Moreover, upregulated autophagy in platelets promotes platelet activation by decreasing hemostasis and thrombus formation [55], which reduce the number of platelets and shorten the lifespan of platelets [56].…”

Section: Discussionmentioning

confidence: 99%

“…Complete autophagic ux, from the formation of autophagosomes to autophagic degradation, is important for the number, size, and activation of platelets and could be a potential therapeutic target for hemorrhagic and thrombosis diseases [55]. Moreover, upregulated autophagy in platelets promotes platelet activation by decreasing hemostasis and thrombus formation [55], which reduce the number of platelets and shorten the lifespan of platelets [56]. Whether SFTSV infection induces complete autophagic ux in human platelets needs to be veri ed.…”

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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“…The latest study showed that P2RY12 receptor inhibits autophagy and reduces cholesterol e uence, promoting VSMC-derived foam cytogenic in advanced atherosclerosis (22). In addition, autophagy has been stated to play an essential role in bleeding and thrombotic diseases by regulating the count and function of PLT, which are the core factors of physiological hemostasia (23). Therefore, it is necessary to conduct clinical or basic experiments to probe the underlying biological functions of these DEARGs.…”

Section: Discussionmentioning

confidence: 99%

Identification and Experimental Validation of Autophagy-Related Genes in Abdominal aortic aneurysm

Yuan

Song

Hai

et al. 2022

Preprint

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Aim Autophagy plays essential roles in abdominal aortic aneurysm (AAA) happening and movement. The objective of this study was to verify the autophagy-related genes (ARGs) underlying AAA empirically and using bioinformatics analysis. Methods Two gene expression profile datasets (GSE98278 and GSE57691) were taken from the GEO database. These datasets were combined and then standardized. The underlying differential expression autophagy-related genes (DEARGs) of AAA were tested using R software. PPIs, associativity, GO enrichment and KEGG pathway functional analyses were used to identify the DEARGs. Finally, qRT-PCR was used to identify the RNA expression levels of the top five hub genes in clinical samples. Results In data from 97 AAA patients and 10 healthy controls, a total of 44 DEARGs (6 up-regulated expressed genes and 38 down-regulated expressed genes) were classified. PPI results showed that these ARGs interact. GO and KEGG enrichment analyses were directed to elucidate the bio-functional of DEARGs. qRT-PCR results presented that the expressed of IL6, PPARG, SOD1 and MAP1LC3B in AAA cases and negative control were in accordance with the bioinformatic analysis results. Conclusion Hub genes such as IL6, PPARG, SOD1 and MAP1LC3B may influence the happening of AAA by controlling autophagy. These findings enhance interpretation of AAA and may be helpful in its diagnosis and treatment.

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Autophagic regulation of platelet biology

Cited by 12 publications

References 56 publications

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia

Hydrogen Sulfide Promotes Platelet Autophagy via PDGFR-α/PI3K/Akt Signaling in Cirrhotic Thrombocytopenia

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

Identification and Experimental Validation of Autophagy-Related Genes in Abdominal aortic aneurysm

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