Kidney Injury Molecule-1 (Kim-1) expression in murine polycystic kidney disease

Kidney Injury Molecule-1 (Kim-1) is a type 1 membrane protein maximally upregulated in proliferating and de-differentiated tubular cells after renal ischemia. Since epithelial dedifferentiation, proliferation and local ischemia may play a role in the pathophysiology of autosomal dominant polycystic kidney disease (ADPKD), we investigated Kim-1 expression in a mouse model of this disease. In the Pkd2 mouse model for ADPKD, cystic kidneys show markedly upregulated Kim-1 levels compared to 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 α-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 de-differentiation of epithelial cells and may play a role in the development of interstitial fibrosis.