Abnormal tenascin expression in murine autosomal recessive polycystic kidneys

The mechanisms responsible for renal cyst formation in congenital polycysti c kidney disease (PKD) remain unknown. Changes in extracellular matrix (ECM ) are regarded as an important pathogenic factor in PKD. Tenascin, an ECM g lycoprotein implicated in abnormal growth in adult organs, has not been sys tematically evaluated in PKD. In this study, tenascin expression was studie d by immunohistochemistry in the autosomal recessive polycystic kidneys of C57BL/6J (cpk/cpk) mice. Scanning electron microscopy was performed to dete rmine the cyst types and their temporal evolution, and to establish correla tions with the immunohistochemistry observations. Cystic lesions evolved in three main stages. Initially, the cysts appeared as segmental dilatations of both proximal and collecting ducts. In the second stage, the collecting duct cysts (CDCs) underwent rapid growth that led to the destruction of all other kidney elements. In the final stage, the CDCs reached their maximum size and the PKD mice died. Normal differentiated principal cells and three types of intercalated cells were present in the CDC epithelium. In all thr ee stages an intense tenascin expression was detected selectively in the ba sement membranes of the cysts. In the last stage, an intense tenascin immun oreactivity was also observed in the interstitial fibrotic tissue. The abno rmal presence of tenascin in the basement membranes of the cysts suggests t hat this glycoprotein is implicated in the pathogenesis of the cysts, possi bly by stimulating cell proliferation.