Kidney injury molecule-1 expression in murine polycystic kidney disease

被引:108
作者
Kuehn, EW
Park, KM
Somlo, S
Bonventre, JV
机构
[1] Massachusetts Gen Hosp E, Renal Unit, Charlestown, MA 02129 USA
[2] Massachusetts Gen Hosp E, Dept Med, Charlestown, MA 02129 USA
[3] Yale Univ, Sch Med, Nephrol Sect, New Haven, CT 06519 USA
[4] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA
关键词
Na-K-ATPase; cell polarity; fibrosis; Tim; ischemia; kidney obstruction;
D O I
10.1152/ajprenal.00166.2002
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Kidney injury molecule-1 (Kim-1) is a type 1 membrane protein maximally upregulated in proliferating and dedifferentiated tubular cells after renal ischemia. Because epithelial dedifferentiation, proliferation, and local ischemia may play a role in the pathophysiology of autosomal dominant polycystic kidney disease, we investigated Kim-1 expression in a mouse model of this disease. In the Pkd2(WS25/-) mouse model for autosomal dominant polycystic kidney disease, cystic kidneys show markedly upregulated Kim-1 levels compared with noncystic control kidneys. Kim-1 is present in a subset of cysts of different sizes and segmental origins and in clusters of proximal tubules near cysts. Kim-1-expressing tubular cells show decreased complexity and quantity of basolateral staining for Na-K-ATPase. Other changes in polarity characteristic of ischemic injury are not present in Kim-1-expressing pericystic tubules. Polycystin-2 expression is preserved in Kim-1-expressing tubules. The interstitium surrounding Kim-1-expressing tubules shows high proliferative activity and staining for smooth muscle alpha-actin, characteristic of myofibroblasts. Although the functional role of the protein in cysts remains unknown, Kim-1 expression in tubules is strongly associated with partial dedifferentiation of epithelial cells and may play a role in the development of interstitial fibrosis.
引用
收藏
页码:F1326 / F1336
页数:11
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