Reversibility of Structural and Functional Damage in a Model of Advanced Diabetic Nephropathy
Reversibility of Structural and Functional Damage in a Model of Advanced Diabetic Nephropathy
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DOI：
10.1681/asn.2012050445
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发表时间：
2013-07-01
影响因子：
13.6
通讯作者：
Alpers, Charles E.
中科院分区：
文献类型：
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作者：
Pichaiwong, Warangkana;Hudkins, Kelly L.;Alpers, Charles E.
糖尿病肾病的可逆性仍存在争议。在这里，我们测试了替代瘦素是否可以逆转由瘦素缺陷的BTBR ob/ob小鼠建模的晚期糖尿病肾病。瘦素替代，但不抑制肾素-血管紧张素-醛固酮系统（RAAS），导致几乎完全逆转的结构（系膜基质扩张，系膜溶解，基底膜增厚，足细胞损失）和功能（蛋白尿，活性氧积累）的措施，先进的糖尿病肾病。免疫组织化学标记的足细胞标志物肾母细胞瘤1和p57确定壁上皮细胞作为再生足细胞的可能来源。因此，瘦素缺陷型BTBR ob/ob小鼠为进一步研究提供了晚期但可逆的糖尿病肾病模型。这些结果还表明，丢失的足细胞的恢复是可能的，但不是由RAAS抑制诱导的，这可能解释了RAAS抑制剂在促进糖尿病肾病修复中的有限功效。
The reversibility of diabetic nephropathy remains controversial. Here, we tested whether replacing leptin could reverse the advanced diabetic nephropathy modeled by the leptin-deficient BTBR ob/ob mouse. Leptin replacement, but not inhibition of the renin-angiotensin-aldosterone system (RAAS), resulted in near-complete reversal of both structural (mesangial matrix expansion, mesangiolysis, basement membrane thickening, podocyte loss) and functional (proteinuria, accumulation of reactive oxygen species) measures of advanced diabetic nephropathy. Immunohistochemical labeling with the podocyte markers Wilms tumor 1 and p57 identified parietal epithelial cells as a possible source of regenerating podocytes. Thus, the leptin-deficient BTBR ob/ob mouse provides a model of advanced but reversible diabetic nephropathy for further study. These results also suggest that restoration of lost podocytes is possible but is not induced by RAAS inhibition, possibly explaining the limited efficacy of RAAS inhibitors in promoting repair of diabetic nephropathy.