Lu Bo, Xing Li, Zhu Xiang-Yang, Tang Hui, Lu Brandon, Yuan Fei, Almasry Yazan, Krueger Alexander, Barsom Samer H, Krier James D, Jordan Kyra L, Lerman Amir, Eirin Alfonso, Lerman Lilach O
Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
Department of Cardiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Shanghai 200437, China.
iScience. 2024 Nov 22;27(12):111454. doi: 10.1016/j.isci.2024.111454. eCollection 2024 Dec 20.
Kidney tissue injury in renal artery stenosis (RAS) involves inflammation, endoplasmic reticulum stress (ERS), and mitochondria damage. Tumor necrosis factor-stimulated gene-6 (TSG-6), an endogenous reparative molecule, may decrease ERS and improve renal function. To assess its impact on the stenotic murine kidney, we injected TSG-6 or vehicle for two weeks in mice with RAS. At completion, we assessed stenotic kidney function and oxygenation, inflammation, and expression of ERS-related genes. TSG-6 treatment reduced renal hypoxia, urinary protein and plasma creatinine levels, renal fibrosis, and apoptosis. TSG-6 also exhibited an anti-inflammatory effect, reflected in the downregulated expression of the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB) pathway in murine kidneys and HK-2 cells . Moreover, ERS-related molecules were downregulated after TSG-6 treatment, while most indicators of mitochondrial unfolded protein response remained unaltered. Therefore, TSG-6 alleviates inflammation, ERS, apoptosis, and fibrosis in the post-stenotic mouse kidney. These observations position TSG-6 as a potential therapeutic tool in RAS.
肾动脉狭窄（RAS）中的肾组织损伤涉及炎症、内质网应激（ERS）和线粒体损伤。肿瘤坏死因子刺激基因6（TSG-6）是一种内源性修复分子，可能会减轻ERS并改善肾功能。为了评估其对狭窄小鼠肾脏的影响，我们在患有RAS的小鼠中注射TSG-6或赋形剂两周。实验结束时，我们评估了狭窄肾脏的功能、氧合、炎症以及ERS相关基因的表达。TSG-6治疗降低了肾脏缺氧、尿蛋白和血浆肌酐水平、肾纤维化和细胞凋亡。TSG-6还表现出抗炎作用，这体现在小鼠肾脏和HK-2细胞中Toll样受体4（TLR4）/核因子κB（NF-κB）通路的表达下调。此外，TSG-6治疗后ERS相关分子下调，而线粒体未折叠蛋白反应的大多数指标保持不变。因此，TSG-6可减轻狭窄后小鼠肾脏的炎症、ERS、细胞凋亡和纤维化。这些观察结果表明TSG-6是RAS的一种潜在治疗工具。
