Chun-Yan Wang1,2, Sai Ma2, Shao-Jie Bi3, Le Su4, Shu-Ya Huang4, Jun-Ying Miao4, Chun-Hong Ma5, Cheng-Jiang Gao5, Ming Hou6,7, Jun Peng2,8. 1. Department of Geriatric Medicine, Second Hospital of Shandong University, Ji'nan 250033, China. 2. Department of Hematology, Qilu Hospital, Shandong University, Ji'nan 250012, China. 3. Department of Cardiology, Second Hospital of Shandong University, Ji'nan 250033, China. 4. Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Science, Shandong University, Ji'nan 250013, China. 5. Department of Immunology, Shandong University School of Medicine, Ji'nan 250012, China. 6. Leading Research Group of Scientific Innovation, Department of Science and Technology of Shandong Province, Ji'nan 250012, China. 7. Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Ji'nan 250012, China. 8. Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital, Shandong University, Ji'nan 250012, China.
Abstract
BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder and involves increased apoptosis of platelets. Autophagy is an essential process for platelets to maintain their life and physiological functions. However, the role of autophagy in ITP platelets was previously unclear. METHODS: In the present study, the expression of autophagy-related protein and autophagy flux were detected in platelets from ITP patients and healthy controls by immunofluorescence staining and immunoblotting, and the influence of autophagy on the viability and apoptosis of ITP platelets was further explored. RESULTS: We found that platelet autophagy was diminished in ITP patients. Platelet autophagy in ITP was regulated by the PI3K/AKT/mTOR pathway, with mTOR (mammalian target of rapamycin) as a negative regulator and class III PtdIns3K playing a crucial role in the process. Importantly, the small-molecule compound ABO (6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine) enhanced autophagy in ITP platelets. Enhancing platelet autophagy alleviated platelet destruction by inhibiting apoptosis and improving platelet viability. CONCLUSIONS: These results suggest a role for autophagy regulation in the pathogenesis of ITP, and offer a novel treatment for these patients.
BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder and involves increased apoptosis of platelets. Autophagy is an essential process for platelets to maintain their life and physiological functions. However, the role of autophagy in ITP platelets was previously unclear. METHODS: In the present study, the expression of autophagy-related protein and autophagy flux were detected in platelets from ITP patients and healthy controls by immunofluorescence staining and immunoblotting, and the influence of autophagy on the viability and apoptosis of ITP platelets was further explored. RESULTS: We found that platelet autophagy was diminished in ITP patients. Platelet autophagy in ITP was regulated by the PI3K/AKT/mTOR pathway, with mTOR (mammalian target of rapamycin) as a negative regulator and class III PtdIns3K playing a crucial role in the process. Importantly, the small-molecule compound ABO (6-amino-2,3-dihydro-3-hydroxymethyl-1,4-benzoxazine) enhanced autophagy in ITP platelets. Enhancing platelet autophagy alleviated platelet destruction by inhibiting apoptosis and improving platelet viability. CONCLUSIONS: These results suggest a role for autophagy regulation in the pathogenesis of ITP, and offer a novel treatment for these patients.
Authors: Mayank Batra; Runxia Tian; Chongxu Zhang; Emile Clarence; Camila Sofia Sacher; Justin Nestor Miranda; Justin Rafa O De La Fuente; Megan Mathew; Desmond Green; Sayari Patel; Maria Virginia Perez Bastidas; Sara Haddadi; Mukunthan Murthi; Miguel Santiago Gonzalez; Shweta Kambali; Kayo H M Santos; Huda Asif; Farzaneh Modarresi; Mohammad Faghihi; Mehdi Mirsaeidi Journal: Sci Rep Date: 2021-02-10 Impact factor: 4.379
Authors: Vivianne S Nelson; Anne-Tess C Jolink; Sufia N Amini; Jaap Jan Zwaginga; Tanja Netelenbos; John W Semple; Leendert Porcelijn; Masja de Haas; Martin R Schipperus; Rick Kapur Journal: Cells Date: 2021-11-19 Impact factor: 6.600