Department of Dermatology, First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China.
Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Ecotoxicol Environ Saf. 2022 Oct 1;244:114020. doi: 10.1016/j.ecoenv.2022.114020. Epub 2022 Aug 29.
Occupational medicamentose-like dermatitis due to trichloroethylene (OMDT) is a key but unresolved question. OMDT patients often present multiple organ damage, including kidney damage. However, the underlying mechanism remains unknown. The purpose of our study was to explore the effect of tubule-specific C5b-9 deposition induced by TCE sensitization on renal tubular ferroptosis and its mechanism. By analyzing pathological changes of TCE-sensitization-mice kidney, we observed a significant renal tubular ferroptosis, which was alleviated by CD59, a C5b-9 inhibitory protein. Moreover, this phenomenon was also replicated in a C5b-9-attacked HK-2 cell model. Further experiments identified that C5b-9 induced cytosolic Ca overload in renal tubular epithelia cells from TCE-sensitization-mice and HK-2 cells. Furthermore, in vitro experiments showed that BAPTA-AM, an intracellular Ca chelator, could rescued ferroptosis induced by C5b-9 in HK-2 cells. Taken together, TCE sensitization induced renal tubular ferroptosis is mediated by C5b-9 and cytosolic Ca overload may play a key role.
职业性药物性皮炎样皮炎（OMDT）是一个关键但未解决的问题。OMDT 患者常表现为多器官损伤，包括肾脏损伤。然而，其潜在机制尚不清楚。本研究旨在探讨 TCE 致敏引起的小管特异性 C5b-9 沉积对肾小管铁死亡的影响及其机制。通过分析 TCE 致敏小鼠肾脏的病理变化，我们观察到明显的肾小管铁死亡，C5b-9 抑制蛋白 CD59 可减轻这种铁死亡。此外，这种现象在 C5b-9 攻击的 HK-2 细胞模型中也得到了复制。进一步的实验确定，C5b-9 诱导 TCE 致敏小鼠和 HK-2 细胞肾小管上皮细胞的胞质 Ca 超载。此外，体外实验表明，胞内 Ca 螯合剂 BAPTA-AM 可挽救 C5b-9 诱导的 HK-2 细胞铁死亡。综上所述，TCE 致敏诱导的肾小管铁死亡是由 C5b-9 介导的，胞质 Ca 超载可能起关键作用。
