Adiponectin Promotes Functional Recovery after Podocyte Ablation
Adiponectin Promotes Functional Recovery after Podocyte Ablation
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DOI：
10.1681/asn.2012040414
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发表时间：
2013-02-01
影响因子：
13.6
通讯作者：
Scherer, Philipp E.
中科院分区：
文献类型：
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作者：
Rutkowski, Joseph M.;Wang, Zhao V.;Scherer, Philipp E.
低水平的脂肪细胞分泌蛋白脂联素与小鼠和人类的蛋白尿相关，但脂联素是否在调节肾脏疾病中起致病作用尚不清楚。在这里，我们首先产生了一种小鼠模型，该模型允许在注射构建体特异性试剂后特异性地在足细胞中诱导胱天蛋白酶-8介导的凋亡。这些POD-ATTAC小鼠表现出显著的肾损伤，模拟人类肾脏疾病的方面，如足突消失、系膜扩张和肾小球硬化。初始诱导后，足细胞和滤过功能均恢复。接下来，我们将POD-ATTAC小鼠与缺乏或过表达脂联素的小鼠杂交。缺乏脂联素的POD-ATTAC小鼠出现不可逆的蛋白尿和肾衰竭;相反，过表达脂联素的POD-ATTAC小鼠恢复更快，间质纤维化程度更低。总之，这些结果表明脂联素是足细胞损伤后的肾脏保护蛋白。此外，POD-ATTAC小鼠为进一步研究提供了一个平台，允许足细胞损伤和再生的精确定时。J Am Soc Nephrol 24：268-282，2013. doi：10.1681/ASN.2012040414
Low levels of the adipocyte-secreted protein adiponectin correlate with albuminuria in both mice and humans, but whether adiponectin has a causative role in modulating renal disease is unknown. Here, we first generated a mouse model that allows induction of caspase-8-mediated apoptosis specifically in podocytes upon injection of a construct-specific agent. These POD-ATTAC mice exhibited significant kidney damage, mimicking aspects of human renal disease, such as foot process effacement, mesangial expansion, and glomerulosclerosis. After the initial induction, both podocytes and filtration function recovered. Next, we crossed POD-ATTAC mice with mice lacking or overexpressing adiponectin. POD-ATTAC mice lacking adiponectin developed irreversible albuminuria and renal failure; conversely, POD-ATTAC mice overexpressing adiponectin recovered more rapidly and exhibited less interstitial fibrosis. In conclusion, these results suggest that adiponectin is a renoprotective protein after podocyte injury. Furthermore, the POD-ATTAC mouse provides a platform for further studies, allowing precise timing of podocyte injury and regeneration. J Am Soc Nephrol 24: 268-282, 2013. doi: 10.1681/ASN.2012040414