syndecan -1介导的VEGF-A加载到细胞外小泡中，促进了aki向ckd过渡期间小管周围毛细血管的修复

IF 4.1 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2025-06-09 DOI:10.1016/j.isci.2025.112862

Xin Zhong , Tao-Tao Tang , Yue Zhang , Ding-Ding Xue , An-Ran Shen , Ning Li , Min Wu , Bi-Cheng Liu , Lin-Li Lv

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引用次数: 0

摘要

急性肾损伤（AKI）是一种严重的临床事件，具有向慢性肾脏疾病（CKD）过渡的高风险。由小管周围毛细血管（ptc）损失引起的持续缺氧是导致这种慢性转变的关键因素。然而，控制ptc损伤和修复的机制，特别是在不同AKI严重程度下，仍不清楚。本研究表明，小细胞外囊泡（sEV）携带VEGF-A作为ptc修复的重要调节因子，并随着小管损伤严重程度的增加而减少。我们发现VEGF-A在中度AKI中通过syndecan-1 （SDC-1）被分类到sEV中，并附着在硫酸肝素链上。肾小管中SDC-1敲低可显著减少VEGF-A向ev的包装，加重ptc的稀薄和肾纤维化。SDC-1的过表达促进了VEGF-A+ sEV的产生及其对内皮细胞的增殖作用。这些发现表明，SDC-1有助于中度损伤小管分泌VEGF-A+ sEV，促进AKI后ptc的修复。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Syndecan-1-mediated loading of VEGF-A into small extracellular vesicles facilitates peritubular capillary repair during AKI-to-CKD transition

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Syndecan-1-mediated loading of VEGF-A into small extracellular vesicles facilitates peritubular capillary repair during AKI-to-CKD transition

Acute kidney injury (AKI) is a severe clinical event with a high risk of transitioning to chronic kidney disease (CKD). Persistent hypoxia resulting from peritubular capillaries (PTCs) loss is a key factor driving this chronic transition. However, the mechanisms governing PTCs injury and repair, particularly under different AKI severity, remain unclear. This study demonstrates that small extracellular vesicle (sEV) carried VEGF-A as an essential regulator of PTCs repair and decreased as the severity of tubular injury increased. We found that VEGF-A was sorted into sEV via syndecan-1 (SDC-1), attaching to the heparan sulfate chain in moderate AKI. SDC-1 knockdown in renal tubules significantly reduced VEGF-A packaging into EVs and aggravated PTCs rarefaction and renal fibrosis. Overexpression of SDC-1 promoted the production of VEGF-A⁺ sEV and their proliferative effects on endothelial cells. These findings demonstrate that SDC-1 contributes to the secretion of VEGF-A⁺ sEV from moderately injured tubules, facilitating PTCs repair after AKI.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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