LPS-induced vein endothelial cell injury and acute lung injury have Btk and Orai 1 to regulate SOC-mediated calcium influx
| Autor: | Xiaochen Qiu, Hengyu Li, Xiaobo Liang, Rongju Sun |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lipopolysaccharides Male ORAI1 Protein Immunology Acute Lung Injury chemistry.chemical_element Apoptosis Lung injury Calcium Calcium in biology 03 medical and health sciences 0302 clinical medicine Agammaglobulinaemia Tyrosine Kinase Human Umbilical Vein Endothelial Cells Immunology and Allergy Bruton's tyrosine kinase Animals Humans Inositol 1 4 5-Trisphosphate Receptors Calcium Signaling Lung TRPC Cells Cultured Calcium signaling Pharmacology biology Chemistry Phospholipase C gamma Endothelial Cells Cell biology Endothelial stem cell Mice Inbred C57BL Disease Models Animal 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Tyrosine kinase |
| Zdroj: | International immunopharmacology. 90 |
| ISSN: | 1878-1705 |
| Popis: | Patients with sepsis and sepsis-related complications have a high mortality. Endothelial cell dysfunction plays a central role in sepsis pathophysiological process. In sepsis patients, endothelial cell apoptosis is associated with intracellular calcium overload. Multiple functions in the apoptotic process have been found to be regulated by calcium signaling. Our previous work had proved that LPS-induced cell injury was associated with store-operated calcium (SOC) entry mediated by stromal interaction molecule-1 (STIM 1) in Human umbilical vein endothelial cells (HUVEC), but the underlying molecular mechanism has not been adequately defined. Here we report that the LPS-induced cell injury is related to the calcium overload in HUVEC. SOC entry mediated by calcium release-activated calcium modulator (Orai) 1 and transient receptor potential canonical (TRPC) 1 was associated with LPS-induced calcium overload and cell apoptosis. Bruton's tyrosine kinase (Btk)/Phospholipase C(PLC) γ/inositol 1,4,5-triphosphate receptor (IP3R) played a major role in regulating calcium overload in LPS-induced HUVEC. Knockdown of Btk markedly inhibited the expressions of Orai 1 and its downstream molecule IP3R but not that of TRPC1 in LPS-induced HUVEC. In mice, knockdown of Btk and Orai 1 inhibited LPS-induced calcium overload, pulmonary vascular endothelial cell (VEC) injury and acute lung injury. These findings demonstrated that Btk acts as a regulator of calcium-dependent signaling, especially in the Orai 1-mediated SOC entry of the LPS-induced VEC. |
| Databáze: | OpenAIRE |
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