Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mechanisms responsible for renal cyst formation in congenital polycystic kidney disease (PKD) remain unknown. Changes in extracellular matrix (ECM) are regarded as an important pathogenic factor in PKD. Tenascin, an ECM glycoprotein implicated in abnormal growth in adult organs, has not been systematically evaluated in PKD. In this study, tenascin expression was studied by immunohistochemistry in the autosomal recessive polycystic kidneys of C57BL/6J (cpk/cpk) mice. Scanning electron microscopy was performed to determine the cyst types and their temporal evolution, and to establish correlations 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 three stages an intense tenascin expression was detected selectively in the basement membranes of the cysts. In the last stage, an intense tenascin immunoreactivity was also observed in the interstitial fibrotic tissue. The abnormal presence of tenascin in the basement membranes of the cysts suggests that this glycoprotein is implicated in the pathogenesis of the cysts, possibly by stimulating cell proliferation.
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PMID:Abnormal tenascin expression in murine autosomal recessive polycystic kidneys. 1039 99

Rodent models of polycystic kidney disease (PKD) have provided valuable insight into the cellular changes associated with cystogenesis in humans. The present study characterizes the morphology of renal and extrarenal pathology of autosomal recessive PKD induced by the wpk gene in Wistar rats. In wpk(-/-) rats, proximal tubule and collecting duct cysts develop in utero and eventually consume the kidney. Increased apoptosis, mitosis, and extracellular tenascin deposition parallel cyst development. Extrarenal pathology occurs in the immune system (thymic and splenic hypoplasia) and central nervous system (CNS; hypoplasia to agenesis of the corpus callosum with severe hydrocephalus). Severity of hydrocephalus varied inversely with size of the corpus callosum. In wpk(-/-) rats, the corpus callosum exhibits relatively few axons that cross the midline. This CNS pathology is similar to that described in three human renal cystic syndromes: orofaciodigital, genitopatellar, and cerebrorenal-digital syndromes. Collecting duct and ventricular ependymal cilia appear morphologically normal. To determine if rodent background strain and the presence of modifier genes affect severity of the disease, we crossed the Wistar-wpk rat with Brown Norway (BN) and Long Evan (LE) rats and found the degree of renal and cerebral pathology was diminished as evidenced by lower kidney weight as a percent of body weight and serum urea nitrogen concentration in cystic rats on LE or BN strains as well as less prominent cranial enlargement. Crosses with BN rats allowed us to localize the wpk gene on chromosome 5 very close to the D5Rat73 marker. The wpk gene lies within a chromosomal region known to harbor a PKD modifier locus. In summary, the types of renal and cerebral pathology seen in the Wistar wpk rat are a unique combination seen only in this rodent model.
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PMID:Development of multiorgan pathology in the wpk rat model of polycystic kidney disease. 1505 65