Li Xiaoran, Ma Junhai, Shi Wei, Su Yu, Fu Xu, Yang Yanlin, Lu Jianzhong, Yue Zhongjin
Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China; Department of Urology, The First Affiliated Hospital of Anhui Medical University and Institute of Urology, Anhui Medical University, Hefei, China.
Department of Urology, Institute of Urology, Gansu Nephro-Urological Clinical Center, Key Laboratory of Urological Diseases in Gansu Province, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, China.
Oxid Med Cell Longev. 2016;2016:5203801. doi: 10.1155/2016/5203801. Epub 2016 Nov 14.
To investigate whether calcium-sensing receptor (CaSR) plays a role in calcium-oxalate-induced renal injury. HK-2 cells and rats were treated with calcium oxalate (CaOx) crystals with or without pretreatment with the CaSR-specific agonist gadolinium chloride (GdCl) or the CaSR-specific antagonist NPS2390. Changes in oxidative stress (OS) in HK-2 cells and rat kidneys were assessed. In addition, CaSR, extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal protein kinase (JNK), and p38 expression was determined. Further, crystal adhesion assay was performed , and the serum urea and creatinine levels and crystal deposition in the kidneys were also examined. CaOx increased CaSR, ERK, JNK, and p38 protein expression and OS and . These deleterious changes were further enhanced upon pretreatment with the CaSR agonist GdCl but were attenuated by the specific CaSR inhibitor NPS2390 compared with CaOx treatment alone. Pretreatment with GdCl further increased and crystal adhesion and renal hypofunction. In contrast, pretreatment with NPS2390 decreased and crystal adhesion and renal hypofunction. CaOx-induced renal injury is related to CaSR-mediated OS and increased mitogen-activated protein kinase (MAPK) signaling, which subsequently leads to CaOx crystal adhesion.
为研究钙敏感受体（CaSR）在草酸钙诱导的肾损伤中是否发挥作用。将HK - 2细胞和大鼠用草酸钙（CaOx）晶体处理，同时或不预先用CaSR特异性激动剂氯化钆（GdCl）或CaSR特异性拮抗剂NPS2390处理。评估HK - 2细胞和大鼠肾脏中氧化应激（OS）的变化。此外，测定CaSR、细胞外信号调节蛋白激酶（ERK）、c - Jun氨基末端蛋白激酶（JNK）和p38的表达。进一步进行晶体黏附试验，并检测血清尿素和肌酐水平以及肾脏中的晶体沉积。CaOx增加了CaSR、ERK、JNK和p38蛋白表达以及OS。与单独的CaOx处理相比，用CaSR激动剂GdCl预处理后，这些有害变化进一步增强，但被特异性CaSR抑制剂NPS2390减弱。用GdCl预处理进一步增加了晶体黏附以及肾功能减退。相反，用NPS2390预处理降低了晶体黏附以及肾功能减退。CaOx诱导的肾损伤与CaSR介导的OS以及丝裂原活化蛋白激酶（MAPK）信号传导增加有关，这随后导致CaOx晶体黏附。
