P2RX1-Involved Glycolytic Metabolism Supports Neutrophil Activation in Acute Pancreatitis
Autor: | Xiao Yuan, Dadong Liu, Chunhua Dai, Wei-Ting Qin, Xu Wang, Danyi Zhang, Yishu Liu, Xiaoxin Zhang |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine Adoptive cell transfer acute pancreatitis Neutrophils Immunology Gene Expression Inflammation purinergic receptor Biology 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Animals Humans Glycolysis Gene Original Research Mice Knockout Purinergic receptor neutrophil Purinergic signalling medicine.disease Immunohistochemistry Receptors Purinergic P2X1 Disease Models Animal 030104 developmental biology medicine.anatomical_structure Glucose Pancreatitis inflammation Cancer research Disease Progression Acute pancreatitis 030211 gastroenterology & hepatology Disease Susceptibility medicine.symptom lcsh:RC581-607 Pancreas Transcriptome Biomarkers purinergic signaling Signal Transduction |
Zdroj: | Frontiers in Immunology Frontiers in Immunology, Vol 11 (2021) |
ISSN: | 1664-3224 |
Popis: | Acute pancreatitis (AP) is characterized by disordered inflammation of the pancreas, and the underlying mechanisms remain unclear. Purinergic signaling plays crucial roles in initiating and amplifying inflammatory signals. Recent evidence reveals that targeting dysregulated purinergic signaling is promising for treating inflammation-associated diseases. To explore the potential involvement of purinergic signaling in AP, we investigated the expression profiles of purinergic signaling molecules in human and mouse pancreas tissues. Results showed that purinergic receptor P2RX1 was among the most highly expressed genes in both human and mouse pancreas tissues. Genetic ablation or specific antagonism of P2RX1 markedly alleviated inflammatory responses in caerulein-induced AP mice. Bone marrow chimeras and adoptive transfer studies revealed that neutrophil-derived P2RX1 contributed to the inflammatory responses in AP. Further studies demonstrated that P2RX1 promoted neutrophil activation by facilitating glycolytic metabolism. Therefore, our study indicates that purinergic receptor P2RX1 may be a potential therapeutic target to treat disordered inflammation in AP. |
Databáze: | OpenAIRE |
Externí odkaz: |