The standard of age‐related glomerulosclerosis is unclear. Both signal transducer and activator of transcription 3 (STAT3) and autophagy are involved in age‐related kidney disease. Therefore, we aimed to explore the standard, as well as the potential mechanism(s). A total of 44 patients who underwent radical nephrectomy were enrolled. Pearson analysis was performed to investigate the parameters with ages. The patients were divided into the young‐ and aged‐kidney groups. Kidney morphological changes were evaluated by histology staining, senescence was evaluated by senescence‐associated‐β‐galactosidase (SA‐β‐gal) staining, and autophagosome was measured by transmission electron microscopy. Moreover, Western blot and/or immunohistochemistry were accomplished to assess the expression of p16, STAT3, and glycoprotein130 (GP130) and autophagy‐related proteins. Furthermore, human glomerular mesangial cells were administrated with tocilizumab (TCZ) and/or IL‐6, and then the above indexes were tested again. Sclerotic glomerular density and glomerular sclerosis rate were significantly higher in individuals more than 40 years old, and they were strongly correlated with ages. Moreover, the expression of p16, STAT3, GP130, and p62 was significantly increased, while LC3II and autophagosome were statistically decreased in the aged‐kidney. Glomeruli were hardly to stain with SA‐β‐gal. For the in vitro experiments, we observed that IL‐6 significantly increased p16, STAT3, GP130, and p62, induced higher SA‐β‐gal staining, while downregulated LC3II and autophagosome. Furthermore, TCZ statistically reversed the effects of IL‐6 on the above expression of proteins. Glomerular sclerosis rate might be one standard for natural renal aging, and IL‐6/STAT3‐mediated autophagy may participate in the development of age‐related glomerulosclerosis.

中文翻译：

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IL-6 / STAT3介导的自噬参与与年龄有关的肾小球硬化的发展

年龄相关性肾小球硬化的标准尚不清楚。信号转导子和转录激活因子3（STAT3）以及自噬均与年龄相关的肾脏疾病有关。因此，我们旨在探索该标准以及潜在的机制。共有44例行根治性肾切除术的患者入选。进行了Pearson分析以调查随年龄变化的参数。将患者分为年轻肾脏组和老年肾脏组。通过组织学染色评估肾脏的形态变化，通过衰老相关的β-半乳糖苷酶（SA-β-gal）染色评估衰老，并通过透射电子显微镜测量自噬体。此外，已完成蛋白质印迹和/或免疫组化实验以评估p16，STAT3，糖蛋白130（GP130）和自噬相关蛋白。此外，对人肾小球系膜细胞给予托珠单抗（TCZ）和/或IL-6，然后再次测试上述指标。40岁以上的人的硬化性肾小球密度和肾小球硬化率显着较高，并且与年龄密切相关。此外，在老年肾脏中，p16，STAT3，GP130和p62的表达显着增加，而LC3II和自噬体的表达显着降低。肾小球几乎不被SA-β-gal染色。对于体外实验，我们观察到IL-6显着增加p16，STAT3，GP130和p62，诱导更高的SA-β-gal染色，同时下调LC3II和自噬体。此外，TCZ在统计学上逆转了IL-6对上述蛋白质表达的影响。肾小球硬化率可能是自然肾衰老的标准之一，IL-6 / STAT3介导的自噬可能参与了与年龄有关的肾小球硬化的发展。