Abstract：
Acute kidney injury (AKI), characterized by a sudden decline in kidney function involving tubular damage and epithelial cell death, can lead to progressive tissue fibrosis and chronic kidney disease due to interstitial fibroblast activation and tissue repair failures that lack direct treatments. After an AKI episode, surviving renal tubular cells undergo cycles of dedifferentiation, proliferation and redifferentiation while fibroblast activity increases and then declines to avoid an exaggerated extracellular matrix deposition. Appropriate tissue recovery versus pathogenic fibrotic progression depends on fine-tuning all these processes. Identifying endogenous factors able to affect any of them may offer new therapeutic opportunities to improve AKI outcomes. Galectin-8 (Gal-8) is an endogenous carbohydrate-binding protein that is secreted through an unconventional mechanism, binds to glycosylated proteins at the cell surface and modifies various cellular activities, including cell proliferation and survival against stress conditions. Here, using a mouse model of AKI induced by folic acid, we show that pre-treatment with Gal-8 protects against cell death, promotes epithelial cell redifferentiation and improves renal function. In addition, Gal-8 decreases fibroblast activation, resulting in less expression of fibrotic genes. Gal-8 added after AKI induction is also effective in maintaining renal function against damage, improving epithelial cell survival. The ability to protect kidneys from injury during both pre- and post-treatments, coupled with its anti-fibrotic effect, highlights Gal-8 as an endogenous factor to be considered in therapeutic strategies aimed at improving renal function and mitigating chronic pathogenic progression.
摘要：
急性肾损伤(AKI),以肾功能突然下降为特征，涉及肾小管损伤和上皮细胞死亡，由于间质成纤维细胞活化和缺乏直接治疗的组织修复失败，可导致进行性组织纤维化和慢性肾病。在AKI事件之后,存活的肾小管细胞经历去分化周期,增殖和再分化，而成纤维细胞活性增加，然后下降，以避免过度的细胞外基质沉积。适当的组织恢复与致病性纤维化进展取决于所有这些过程的微调。识别能够影响它们中的任何一个的内源性因素可能为改善AKI结果提供新的治疗机会。半乳糖凝集素-8（Gal-8）是一种内源性碳水化合物结合蛋白，通过非常规机制分泌，与细胞表面的糖基化蛋白质结合并修饰各种细胞活性，包括细胞增殖和在应激条件下的存活。这里,使用叶酸诱导的AKI小鼠模型，我们表明用Gal-8预处理可以防止细胞死亡，促进上皮细胞再分化，改善肾功能。此外,Gal-8减少成纤维细胞活化，导致纤维化基因表达减少。在AKI诱导后添加Gal-8也有效维持肾功能抵抗损伤，提高上皮细胞的存活率。在治疗前后保护肾脏免受损伤的能力，再加上它的抗纤维化作用，强调Gal-8是一种内源性因子，在旨在改善肾功能和缓解慢性致病进展的治疗策略中需要考虑。
