Zag Expression during Aging Suppresses Proliferation after Kidney Injury
Zag Expression during Aging Suppresses Proliferation after Kidney Injury
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DOI：
10.1681/asn.2008010035
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发表时间：
2008-12-01
影响因子：
13.6
通讯作者：
Cantley, Lloyd G.
中科院分区：
文献类型：
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作者：
Schmitt, Roland;Marlier, Arnaud;Cantley, Lloyd G.
老年人急性肾损伤后的恢复受到损害，但关于为什么会发生这种情况的机制信息有限。在这项研究中，衰老的小鼠肾脏在体内和体外都显示出上皮细胞增殖储备减少。基因芯片分析证实，在衰老的近端肾小管细胞中，锌-α(2)-糖蛋白(ZAG)的表达增加。在原代培养的肾上皮细胞中加入重组ZAG可抑制细胞增殖，而敲除ZAG则可促进细胞增殖。在体内，系统的小干扰RNA抑制了小鼠近端小管中ZAG的表达；这增加了老年小鼠肾脏缺血/再灌注后上皮细胞的增殖率，但也增加了实质纤维化。这些结果表明，ZAG在老年肾脏中的表达增加，抑制了对损伤的增殖反应，并引入ZAG作为衰老表型的修饰物。
Recovery after acute kidney injury is impaired in the elderly, but mechanistic information regarding why this occurs is limited. In this study, aged mouse kidneys displayed a reduced epithelial proliferative reserve in vivo and in vitro. Microarray analysis identified increased expression of zinc-alpha (2)-glycoprotein (Zag) in aged proximal tubular cells. The addition of recombinant Zag to primary renal epithelial cell cultures decreased proliferation, whereas knockdown of Zag increased proliferation. In vivo, systemic small interference RNA suppressed expression of Zag in the mouse proximal tubule; this increased the rate of epithelial cell proliferation after renal ischemia/reperfusion in aged mice but also increased parenchymal fibrosis. These results demonstrate that increased Zag expression in the aged kidney acts to suppress the proliferative response to injury and introduce Zag as a modifier of the aging phenotype.