Platelets promote acute liver injury via extracellular vesicles-mediated Aldolase A
Yang, R.; Liu, J.; Fu, K.; Wan, T.; Li, Y.; Shen, C.; Yang, L.; Wang, K.; Shan, Z.
Show abstract
Platelets have emerged as active regulators of acute liver injury (ALI), yet the molecular mechanisms underlying their pathogenic functions remain poorly defined. Here, we demonstrate that platelets exacerbate liver injury by metabolically reprogramming Kupffer cells (KCs). We show that platelets are actively recruited to the injured liver and communicate with KCs through extracellular vesicles (EVs), which deliver the glycolytic enzyme aldolase A (ALDOA) into recipient cells. This EV-mediated transfer induces a robust glycolytic switch in KCs, licensing their pro-inflammatory activation and amplifying hepatic injury. Using platelet-specific Aldoa knockout mice, we establish that platelet-derived ALDOA is essential for KCs metabolic reprogramming and disease progression in vivo. Pharmacological inhibition of ALDOA with Aldometanib markedly attenuated liver injury. Circulating ALDOA levels were elevated in patients with ALI and correlated with disease severity. These findings uncover a platelet-macrophage metabolic axis that drives ALI and nominate ALDOA as a therapeutic target and biomarker.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Hepatic lipopolysaccharide binding protein partially uncouples inflammation from fibrosis in MAFLD 94%
- Liver-specific suppression of ANGPTL4 improves obesity-associated diabetes and mitigates atherosclerosis in mice 94%
- Multiomic Profiling Reveals Metabolic Alterations Mediating Aberrant Platelet Activity and Inflammation in Myeloproliferative Neoplasms 93%
Similar papers in this journal
Similar papers in this journal
- Patient induced pluripotent stem cell-derived hepatostellate organoids establish a basis for liver pathologies in telomeropathies 95%
- CD73 maintains hepatocyte metabolic integrity and mouse liver homeostasis in a sex-dependentmanner 94%
- Regulation of Liver Regeneration by hepatocyte O-GlcNAcylation in mice 94%
Similar papers in this journal
- A spatial map of hepatic mitochondria uncovers functional heterogeneity shaped by nutrient-sensing signaling 95%
- Autocrine IL11 cis-signaling in hepatocytes is an initiating nexus between lipotoxicity and non-alcoholic steatohepatitis 95%
- Loss of embryonically-derived Kupffer cells during hypercholesterolemia accelerates atherosclerosis development 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.