Role of Acid-sensing Ion Channels (ASICs) in the Vascular Endothelial Cells Injury of Henoch- Schonlein Purpura Children

Abstract Objective: Acid-sensing ion channels (ASICs) are cationic channels that are activated by extracellular acidification. ASICs are widely expressed in the peripheral and central nervous systems and participate in many important physiological and pathological processes, such as synaptic plasticity, cerebral ischemia, and pain. Recently accumulating evidence suggests that ASICs can also profoundly affect the physiological properties of non-neural cells. This study was firstly to investigate the expression of ASICs subunits in the vascular endothelial cells of Henoch-Sch？nlein Purpura (HSP) patients and their role in vascular endothelial cell injury following acid exposure. Methods: Human dermal microvascular endothelial cells (HDMECs) were used to establish the model of vascular endothelial cell injury by incubation with IgA1 from HSP patients. The cell injury following acid exposure was analyzed with inflammatory cytokines release assay and cytoskeletal protein destrin, α-skeletal muscle actin (SM-α) changes. The acid- induced ASICs, destrin and SM-α actin mRNA and protein expressions in HDMECs were evaluated by quantitative real-time polymerase chain reaction (qPCR) and western blotting, respectively. The release of inflammatory cytokines interleukin-8 (IL-8), thrombomodulin (TM) and nitric oxide (NO) were analyzed by ELISA methods. Furthermore, we analyzed the relationship between ASICs expression with cytokines release, destrin and SM-α actin levels by Person Correlations. Results: The results showed that extracellular acid could upregulate ASIC1a, ASIC2a and ASIC3 mRNA and protein expression, stimulate IL-8, TM and NO, and decrease destrin and SM -α actin expression in HDMECs pretreated with IgA1 from HSP patients. Furthermore, ASICs expression was positively related to the production of cytokines and negatively related with destrin and SM-α actin expression, respectively. In addition, pharmacological blockade of ASICs attenuated the inflammation response and inhibited the loss of cytoskeletal protein in vascular endothelial cells pretreated with IgA1 from HSP patients. Conclusion: These findings showed that extracellular acid could activate ASICs expression in the vascular endothelial cells pretreated with IgA1 from HSP patients, which induced further endothelial cells damage. Additionally, the inhibitor of ASICs may have a significant protective effect on the inflammatory injury of vascular endothelial cells