Yuan Li-Ping, Bo Yan, Qin Zhang, Ran Hua, Li Wang, Li Yu-Fei, Ming Gui
Department of Pediatrics, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).
Department of Medical Technology, Anhui Medical College, Hefei, Anhui, China (mainland).
Med Sci Monit. 2017 Apr 21;23:1916-1922. doi: 10.12659/msm.904132.
BACKGROUND Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. However, the role of ASICs in kidney diseases remains uncertain. This study investigated ASICs expression in kidney tissues and their role in the development of Henoch-Schönlein purpura nephritis (HSPN). MATERIAL AND METHODS The expression of ASIC subunits was examined by immunochemical techniques in the kidney tissue from HSPN patients. Acid-induced ASICs expression in cultured renal tubular epithelial cells was determined by quantitative RT-PCR analysis. The expression of K7 and K18 protein in renal tubular epithelial cells was used to evaluate acid-induced cell injury. In addition, we observed the effect of blocking ASICs on acid-induced cell injury to assess the role of ASICs in renal tubular epithelial cell injury. RESULTS The results showed that ASIC1, ASIC2, and ASIC3 proteins were obviously expressed in renal tubular cells from HSPN patients. ASIC1 expression and 24-h urine protein level were higher in the pathological grade ISKD III group than in the ISKD II group. ASIC1, ASIC2, and ASIC3 mRNA, and K7 and K18 protein expression in cultured renal tubular epithelial cells were increased when exposed to pH 6.5. K7 and K18 protein expression was closely related to ASIC1 expression, and ASICs blockers reduced K7 and K18 protein expression in tubular epithelial cells. CONCLUSIONS These findings suggest ASICs are most highly expressed in renal tubular cells of HSPN patients, which is closely related to renal tubular injury. ASICs might be involved in the development of HSPN.
背景 酸敏感离子通道（ASICs）是由细胞外质子激活的配体门控阳离子通道。然而，ASICs在肾脏疾病中的作用仍不明确。本研究调查了ASICs在肾脏组织中的表达及其在过敏性紫癜肾炎（HSPN）发病中的作用。
材料与方法 采用免疫化学技术检测HSPN患者肾脏组织中ASIC亚基的表达。通过定量逆转录聚合酶链反应（RT-PCR）分析测定培养的肾小管上皮细胞中酸诱导的ASICs表达。利用肾小管上皮细胞中K7和K18蛋白的表达来评估酸诱导的细胞损伤。此外，我们观察了阻断ASICs对酸诱导的细胞损伤的影响，以评估ASICs在肾小管上皮细胞损伤中的作用。
结果 结果显示，ASIC1、ASIC2和ASIC3蛋白在HSPN患者的肾小管细胞中明显表达。病理分级为ISKD III组的ASIC1表达和24小时尿蛋白水平高于ISKD II组。当暴露于pH 6.5时，培养的肾小管上皮细胞中ASIC1、ASIC2和ASIC3 mRNA以及K7和K18蛋白表达增加。K7和K18蛋白表达与ASIC1表达密切相关，ASICs阻滞剂可降低肾小管上皮细胞中K7和K18蛋白表达。
结论 这些发现表明，ASICs在HSPN患者的肾小管细胞中表达最高，这与肾小管损伤密切相关。ASICs可能参与了HSPN的发病过程。
