Division of Nephrology, Department of Internal Medicine, Taipei Hospital, Ministry of Health and Welfare, New Taipei City, Taiwan.
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan.
Oxid Med Cell Longev. 2022 Mar 27;2022:5696686. doi: 10.1155/2022/5696686. eCollection 2022.
Cigarette smoke (CS) is a risk factor for chronic obstructive pulmonary disease. We attempted to investigate fully the possible effects of CS on kidney cells. We found that the viability of a human kidney proximal tubular epithelial cell line (HK-2 cells) was decreased after treatment with CS extract (CSE). In particular, the effects of CSE at low concentrations did not change the expression of apoptosis and necrosis. Furthermore, CSE increased autophagy- and fibrosis-related proteins in HK-2 cells. Senescence-related proteins and the senescence-associated secretory phenotype (SASP) increased after HK-2 cells were treated with CSE. In addition, both RNA sequencing and gene set enrichment analysis data revealed that glucose-6-phosphate dehydrogenase (G6PD) in the reactive oxygen species (ROS) pathway is responsible for the changes in CSE-treated HK-2 cells. CSE increased G6PD expression and its activity. Moreover, the inhibition of G6PD activity increased senescence in HK-2 cells. The inhibition of autophagy reinforced senescence in the CSE-treated cells. In a mouse model of CS exposure, CS caused kidney damage, including tubular injury and glomerulosclerosis. CS increased fibrosis, autophagy, and G6PD expression in kidney tissue sections. In conclusion, CS induced G6PD expression, autophagy, fibrosis, and senescence in kidney cells. G6PD has a protective role in CS-induced nephrotoxicity.
香烟烟雾（CS）是慢性阻塞性肺疾病的一个风险因素。我们试图全面研究 CS 对肾脏细胞的可能影响。我们发现，CS 提取物（CSE）处理后，人肾近端管状上皮细胞系（HK-2 细胞）的活力下降。特别是，CSE 在低浓度时的作用不会改变细胞凋亡和坏死的表达。此外，CSE 增加了 HK-2 细胞中的自噬和纤维化相关蛋白。CSE 处理后的 HK-2 细胞中衰老相关蛋白和衰老相关分泌表型（SASP）增加。此外，RNA 测序和基因集富集分析数据均表明，活性氧（ROS）途径中的葡萄糖-6-磷酸脱氢酶（G6PD）是 CSE 处理的 HK-2 细胞变化的原因。CSE 增加了 G6PD 的表达和活性。此外，抑制 G6PD 活性增加了 HK-2 细胞的衰老。自噬的抑制加强了 CSE 处理细胞中的衰老。在 CS 暴露的小鼠模型中，CS 导致肾脏损伤，包括肾小管损伤和肾小球硬化。CS 增加了肾组织切片中的纤维化、自噬和 G6PD 表达。总之，CS 诱导了肾脏细胞中的 G6PD 表达、自噬、纤维化和衰老。G6PD 在 CS 诱导的肾毒性中具有保护作用。
