Kidney injury molecule-1 expression in murine polycystic kidney disease.
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.
Kuehn
E Wolfgang
EW
Renal Unit and Department of Medicine, Massachusetts General Hospital, Charlestown 02129, USA.
Park
Kwon Moo
KM
Somlo
Stefan
S
Bonventre
Joseph V
JV
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D004847:Epithelial Cells / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology; D007150:Immunohistochemistry; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000473:pathology; D016891:Polycystic Kidney, Autosomal Dominant / Q000378:metabolism*; D012016:Reference Values; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013194:Staining and Labeling; D050396:TRPP Cation Channels; D014018:Tissue Distribution
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D050396:TRPP Cation Channels; C110936:Havcr1 protein, rat