Permanent genetic tagging of podocytes: Fate of injured podocytes in a mouse model of glomerular sclerosis

被引:66
作者
Asano, T
Niimura, F
Pastan, I
Fogo, AB
Ichikawa, I
Matsusaka, T [1 ]
机构
[1] Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 2591193, Japan
[2] Tokai Univ, Sch Med, Dept Pediat, Isehara, Kanagawa 2591193, Japan
[3] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA
[6] Tokyo Med & Dent Univ, Grad Sch, Dept Pediat & Dev Biol, Bunkyo Ku, Tokyo, Japan
[7] NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA
来源
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2005年 / 16卷 / 08期
关键词
D O I
10.1681/ASN.2004121134
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Injured podocytes lose differentiation markers. Therefore, the true identity of severely injured podocytes remains unverified. A transgenic mouse model equipped with a podocyte-selective injury induction system was established. After induction of podocyte injury, mice rapidly developed glomerulosclerosis, with downregulation of podocyte marker proteins. Proliferating epithelial cells accumulated within Bowman's space, as seen in collapsing glomerulosclerosis. In this study, the fate of injured podocytes was pursued. Utilizing Cre-loxP recombination, the podocyte lineage was genetically labeled with lacZ in an irreversible manner. After podocyte injury, the number of lacZ-labeled cells, which were often negative for synaptopodin, progressively declined, correlating with glomerular damage. Parietal epithelial cells, but not lacZ-labeled podocytes, avidly proliferated. The cells proliferating within Bowman's capsule and, occasionally, on the outer surface of the glomerular basement membrane were lacZ-negative. Thus, when podocytes are severely injured, proliferating parietal epithelial cells migrate onto the visceral site, thereby mimicking proliferating podocytes.
引用
收藏
页码:2257 / 2262
页数:6
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