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

作　　者：Hua-Xiang Yang Yang-Jie Li Yang-Lan He Ke-Ke Jin Ling-Na Lyu Hui-Guo Ding 

机构地区：[1]Department of Gastroenterology and Hepatology,Beijing You’an Hospital Affiliated to Capital Medical University,Beijing,China

出　　处：《Journal of Clinical and Translational Hepatology》2024年第7期625-633,共9页临床与转化肝病杂志（英文版）

摘　　要：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 terachloride-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.

关 键 词：Liver cirrhosis THROMBOCYTOPENIA PLATELET AUTOPHAGY Hydrogen sulfide NaHS PDGFR-Α PI3K/Akt/mTOR signaling 

分 类 号：R575.2[医药卫生—消化系统]