Renal tubular epithelial cells are vulnerable to stress-induced damage, including excessive lipid accumulation and aging, with ANGPTL4 potentially playing a crucial bridging role between these factors. In this study, RNA-sequencing was used to identify a marked increase in ANGPTL4 expression in kidneys of diet-induced obese and aging mice. Overexpression and knockout of ANGPTL4 in renal tubular epithelial cells (HK-2) was used to investigate the underlying mechanism. Subsequently, ANGPTL4 expression in plasma and kidney tissues of normal young controls and elderly individuals was analyzed using ELISA and immunohistochemical techniques. RNA sequencing results showed that ANGPTL4 expression was significantly upregulated in the kidney tissue of diet-induced obesity and aging mice. In vitro experiments demonstrated that overexpression of ANGPTL4 in HK-2 cells led to increased lipid deposition and senescence. Conversely, the absence of ANGPTL4 appears to alleviate the impact of free fatty acids (FFA) on aging in HK-2 cells. Additionally, aging HK-2 cells exhibited elevated ANGPTL4 expression, and stress response markers associated with cell cycle arrest. Furthermore, our clinical evidence revealed dysregulation of ANGPTL4 expression in serum and kidney tissue samples obtained from elderly individuals compared to young subjects. Our study findings indicate a potential association between ANGPTL4 and age-related metabolic disorders, as well as injury to renal tubular epithelial cells. This suggests that targeting ANGPTL4 could be a viable strategy for the clinical treatment of renal aging.

中文翻译：

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肾脂质积累和衰老与 ANGPTL4 引起的肾小管细胞损伤有关

肾小管上皮细胞容易受到应激引起的损伤，包括脂质过度积累和衰老，而 ANGPTL4 可能在这些因素之间发挥重要的桥梁作用。在这项研究中，RNA测序被用来鉴定饮食诱导的肥胖和衰老小鼠肾脏中ANGPTL4表达的显着增加。利用肾小管上皮细胞 (HK-2) 中 ANGPTL4 的过表达和敲除来研究其潜在机制。随后，使用ELISA和免疫组织化学技术分析正常年轻对照和老年人血浆和肾组织中ANGPTL4的表达。 RNA测序结果显示，饮食诱导的肥胖和衰老小鼠的肾组织中ANGPTL4表达显着上调。体外实验表明，HK-2细胞中ANGPTL4的过度表达导致脂质沉积增加和衰老。相反，ANGPTL4 的缺失似乎减轻了游离脂肪酸 (FFA) 对 HK-2 细胞衰老的影响。此外，老化的 HK-2 细胞表现出 ANGPTL4 表达升高，以及与细胞周期停滞相关的应激反应标记物。此外，我们的临床证据显示，与年轻受试者相比，从老年人获得的血清和肾组织样本中 ANGPTL4 表达失调。我们的研究结果表明 ANGPTL4 与年龄相关的代谢紊乱以及肾小管上皮细胞损伤之间存在潜在关联。这表明靶向 ANGPTL4 可能是临床治疗肾脏衰老的可行策略。