Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis.
Glomerular parietal epithelial cells contribute to adult podocyte regeneration in experimental focal segmental glomerulosclerosis.
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DOI：
10.1038/ki.2015.152
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发表时间：
2015-11
影响因子：
19.6
通讯作者：
Shankland SJ
中科院分区：
文献类型：
--
作者：
Eng DG;Sunseri MW;Kaverina NV;Roeder SS;Pippin JW;Shankland SJ
由于成年足细胞在疾病状态下耗尽后无法充分增殖，因此人们对祖细胞在足细胞修复和再生中的潜在作用产生了兴趣。为了确定壁上皮细胞 (PEC) 是否可以在疾病诱导的足细胞耗竭后充当成年足细胞祖细胞，在成年 PECrtTA/LC1/R26 报告小鼠中对 PEC 进行永久标记。在正常小鼠中，标记的 PEC 局限于鲍曼氏囊，而在疾病（细胞毒性羊抗足细胞抗体）中，在第 7、14 和 28 天时，在肾小球簇中发现标记的 PEC 数量逐渐增加。在疾病早期，簇中的大多数 PEC 共表达 CD44。到第 28 天，当足细胞数量显着增加且疾病严重程度显着降低时，大多数标记的 PEC 共表达足细胞蛋白，但不表达 CD44。簇上的标记 PEC 和足细胞都没有进行增殖标记 BrdU 染色。磷酸-ERK 的从头表达与表达 CD44 的 PEC 共定位，但不与表达足细胞标记物的 PEC 共定位。因此，在以足细胞突然耗竭然后再生为代表的局灶节段性肾小球硬化小鼠模型中，PEC一旦迁移到肾小球簇就会经历两种表型变化。最初，这些细胞主要是与肾小球硬化一致的活化的 CD44 表达细胞，后来它们主要表现出可能是修复性的足细胞表型。
Since adult podocytes cannot adequately proliferate following depletion in disease states there has been interest in the potential role of progenitors in podocyte repair and regeneration. To determine if parietal epithelial cells (PECs) can serve as adult podocyte progenitors following disease-induced podocyte depletion, PECs were permanently labeled in adult PECrtTA/LC1/R26 reporter mice. In normal mice, labeled PECs were confined to Bowman's capsule, while in disease (cytotoxic sheep anti-podocyte antibody), labeled PECs were found in the glomerular tuft in progressively higher numbers by days 7, 14 and 28. Early in disease, the majority of PECs in the tuft co-expressed CD44. By day 28, when podocyte numbers were significantly higher and disease severity was significantly lower, the majority of labeled PECs co-expressed podocyte proteins but not CD44. Neither labeled PECs on the tuft, nor podocytes stained for the proliferation marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs undergo two phenotypic changes once they migrate to the glomerular tuft. Initially these cells are predominantly activated CD44 expressing cells coinciding with glomerulosclerosis, and later they predominantly exhibit a podocyte phenotype which is likely reparative.