Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, PR China.
Institute of Dermatology, The First Affiliated Hospital of Anhui Medical University, Hefei, PR China; Key Laboratory of Dermatology, Ministry of Education, The First Affiliated Hospital of Anhui Medical University, Hefei, PR China.
Ecotoxicol Environ Saf. 2022 Sep 15;243:114019. doi: 10.1016/j.ecoenv.2022.114019. Epub 2022 Aug 26.
Patients with trichloroethene-induced Trichloroethylene hypersensitivity syndrome (THS) often present kidney injury. However, the role of Wnt 5a/Ca pathway in renal tubular injury in Trichloroethylene (TCE) sensitized mice remains unclear. This study aimed to investigate how Wnt 5a/Ca pathway induced renal tubular epithelial cell injury in TCE sensitized mice. A total of 84 female BALB/c Specific Pathogen Free mice aged 6-8 weeks were used to establish TCE sensitized mouse models. Renal histology and serum levels of α1-MG and β2-MG were used to assess the renal injury. The renal protein levels of Wnt 5a, ROR2, FZD5, PLC, p-CaMKII, IκB α, p-IκB α, NF-κB(p65), TNF α, IL 6 and IL 1β were measured. The levels of serum α1-MG and β2-MG and TNF α, IL 6 and IL 1β levels in the kidney tissue were significantly increased in TCE sensitized positive group. However, Box5 pretreatment inhibited the expression of PLC, p-CaMKII, p65 and attenuated the injury of renal tubular epithelial cells and suppressed the upregulated expression of the above cytokines. In addition, KN93 also reduced nuclear translocation of p65 and renal injury as well as the elevated cytokines by inhibiting CaMKII. These data identify Wnt 5a binding to ROR2 and FZD5, p65 nuclear translocation, and inflammatory cytokine release as a novel mechanism for renal tubular epithelial cells injury by sensitization with TCE. Box5 or KN93 pretreatment can block the expression of inflammatory cytokines and reduce the injury of renal tubular epithelial cells.
三氯乙烯所致三氯乙烯敏感性综合征（THS）患者常出现肾脏损伤。然而，Wnt5a/Ca 通路在三氯乙烯（TCE）致敏小鼠肾小管损伤中的作用尚不清楚。本研究旨在探讨 Wnt5a/Ca 通路如何诱导 TCE 致敏小鼠肾小管上皮细胞损伤。共使用 84 只 6-8 周龄雌性 BALB/c 无特定病原体小鼠建立 TCE 致敏小鼠模型。采用肾组织学和血清α1-MG 和β2-MG 水平评估肾脏损伤。检测 Wnt5a、ROR2、FZD5、PLC、p-CaMKII、IκBα、p-IκBα、NF-κB（p65）、TNFα、IL-6 和 IL-1β 的肾蛋白水平。TCE 致敏阳性组血清α1-MG 和β2-MG 及 TNFα、IL-6 和 IL-1β 水平显著升高。然而，Box5 预处理抑制了 PLC、p-CaMKII、p65 的表达，减轻了肾小管上皮细胞的损伤，并抑制了上述细胞因子的上调表达。此外，KN93 通过抑制 CaMKII 也减少了 p65 的核易位和肾脏损伤以及升高的细胞因子。这些数据表明，Wnt5a 与 ROR2 和 FZD5 结合、p65 核易位和炎症细胞因子释放是 TCE 致敏引起肾小管上皮细胞损伤的新机制。Box5 或 KN93 预处理可以阻断炎症细胞因子的表达，减少肾小管上皮细胞的损伤。
