constitutive Atg5 过表达可改善小鼠骨髓内皮祖细胞实验性急性肾损伤。
Constitutive Atg5 overexpression in mouse bone marrow endothelial progenitor cells improves experimental acute kidney injury.
机构信息
Zentrum für Innere Medizin 1 - Kardiologie, Angiologie, Nephrologie, Klinikum Brandenburg, Medizinische Hochschule Brandenburg, Klinikum Brandenburg, Hochstraße 29, 14770, Brandenburg, Germany.
Klinik für Nephrologie und Rheumatologie, Universitätsmedizin Göttingen, Göttingen, Germany.
出版信息
BMC Nephrol. 2020 Nov 23;21(1):503. doi: 10.1186/s12882-020-02149-1.
BACKGROUND
Endothelial Progenitor Cells have been shown as effective tool in experimental AKI. Several pharmacological strategies for improving EPC-mediated AKI protection were identified in recent years. Aim of the current study was to analyze consequences of constitutive Atg5 activation in murine EPCs, utilized for AKI therapy.
METHODS
Ischemic AKI was induced in male C57/Bl6N mice. Cultured murine EPCs were systemically injected post-ischemia, either natively or after Atg5 transfection (Adenovirus-based approach). Mice were analyzed 48 h and 6 weeks later.
RESULTS
Both, native and transfected EPCs (EPCs) improved persisting kidney dysfunction at week 6, such effects were more pronounced after injecting EPCs. While matrix deposition and mesenchymal transdifferentiation of endothelial cells remained unaffected by cell therapy, EPCs, particularly EPCs completely prevented the post-ischemic loss of peritubular capillaries. The cells finally augmented the augophagocytic flux in endothelial cells.
CONCLUSIONS
Constitutive Atg5 activation augments AKI-protective effects of murine EPCs. The exact clinical consequences need to be determined.
背景
内皮祖细胞（Endothelial Progenitor Cells）已被证明是治疗急性肾损伤（AKI）的有效工具。近年来，已经确定了几种改善内皮祖细胞介导的 AKI 保护的药理学策略。本研究的目的是分析在用于 AKI 治疗的小鼠内皮祖细胞中持续激活 Atg5 的后果。
方法
在雄性 C57/Bl6N 小鼠中诱导缺血性 AKI。在缺血后，通过系统注射培养的小鼠内皮祖细胞（原生或转染 Atg5 后（基于腺病毒的方法））进行治疗。在 48 小时和 6 周后对小鼠进行分析。
结果
无论是原生的还是转染的内皮祖细胞（EPCs）都能改善 6 周时持续存在的肾功能障碍，而注射 EPCs 的效果更为明显。虽然细胞治疗对基质沉积和内皮细胞的间充质转化没有影响，但 EPCs，特别是 EPCs 完全防止了缺血后肾小管周围毛细血管的丢失。最后，这些细胞增加了内皮细胞中的自噬通量。
结论
持续激活 Atg5 可增强小鼠内皮祖细胞的 AKI 保护作用。确切的临床后果仍需确定。
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