BACKGROUND The matricellular protein periostin has been associated with CKD progression in animal models and human biopsy specimens. Periostin functions by interacting with extracellular matrix components to drive collagen fibrillogenesis and remodeling or by signaling through cell-surface integrin receptors to promote cell adhesion, migration, and proliferation. However, its role in AKI is unknown. METHODS We used mice with conditional tubule-specific overexpression of periostin or knockout mice lacking periostin expression in the renal ischemia-reperfusion injury model, and primary cultures of isolated tubular cells in a hypoxia-reoxygenation model. RESULTS Tubular epithelial cells showed strong production of periostin during the repair phase of ischemia reperfusion. Periostin overexpression protected mice from renal injury compared with controls, whereas knockout mice showed increased tubular injury and deteriorated renal function. Periostin interacted with its receptor, integrin-β1, to inhibit tubular cell cycle arrest and apoptosis in in vivo and in vitro models. After ischemia-reperfusion injury, periostin-overexpressing mice exhibited diminished expression of proinflammatory molecules and had more F4/80+ macrophages compared with knockout mice. Macrophages from periostin-overexpressing mice showed increased proliferation and expression of proregenerative factors after ischemia-reperfusion injury, whereas knockout mice exhibited the opposite. Coculturing a macrophage cell line with hypoxia-treated primary tubules overexpressing periostin, or treating such macrophages with recombinant periostin, directly induced macrophage proliferation and expression of proregenerative molecules. CONCLUSIONS In contrast to the detrimental role of periostin in CKD, we discovered a protective role of periostin in AKI. Our findings suggest periostin may be a novel and important mediator of mechanisms controlling renal repair after AKI.

中文翻译：

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Periostin促进AKI后的细胞增殖和巨噬细胞极化，从而推动修复。

背景技术在动物模型和人类活检样品中，基质细胞蛋白骨膜素与CKD进展有关。骨膜素通过与细胞外基质成分相互作用来驱动胶原纤维形成和重塑，或者通过细胞表面整联蛋白受体发出信号来促进细胞粘附，迁移和增殖而发挥作用。但是，其在AKI中的作用尚不清楚。方法我们在肾缺血-再灌注损伤模型中使用了有条件的肾小管特异性过表达肾小管的小鼠或缺乏骨膜蛋白表达的基因敲除小鼠，在缺氧-再充氧模型中分离了肾小管细胞的原代培养。结果在缺血再灌注的修复阶段，肾小管上皮细胞显示出强烈的骨膜生成。与对照组相比，骨膜素过表达保护小鼠免受肾损伤，而基因敲除小鼠则显示出肾小管损伤增加和肾功能恶化。骨膜素与其受体整合素β1相互作用，在体内和体外模型中抑制肾小管细胞周期停滞和凋亡。缺血再灌注损伤后，与敲除小鼠相比，过表达骨膜素的小鼠的促炎分子表达降低，并且具有更多的F4 / 80 +巨噬细胞。来自过表达骨膜素的小鼠的巨噬细胞在缺血-再灌注损伤后表现出增加的增殖和前再生因子的表达，而基因敲除的小鼠表现出相反的结果。将巨噬细胞细胞系与过表达缺氧的骨膜素处理过的初级小管共培养，或用重组骨膜素处理此类巨噬细胞，直接诱导巨噬细胞增殖和再生分子的表达。结论与骨膜素在CKD中的有害作用相反，我们发现了骨膜素在AKI中的保护作用。我们的发现表明，骨膜素可能是AKI后控制肾脏修复的机制的一种新颖而重要的介质。