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

Claudin-7 and claudin-8 code for tight junction proteins expressed in distal nephron epithelium. In a recent oligonucleotide microarray study, we identified claudin-7 and claudin-8 as candidate markers to distinguish chromophobe renal cell carcinoma from other renal tumors, including oncocytoma. Distinction of these lesions can be difficult by light microscopy but is clinically important because chromophobe renal cell carcinoma has malignant biological potential, whereas renal oncocytoma is benign. Claudin-7 and claudin-8 expression was studied by immunohistochemistry in 11 chromophobe renal cell carcinomas and 17 oncocytomas using formalin-fixed paraffin-embedded tissue sections of tumor with adjacent nonneoplastic kidney. Steam antigen retrieval was performed before immunohistochemistry. Specificity was verified by negative control reactions without primary antibody and appropriate membranous staining patterns in positive control tissues (colon carcinoma and adjacent nonneoplastic kidney). Claudin-7 protein was expressed in a membranous pattern in 10 of 11 chromophobe renal cell carcinomas and 4 of 17 oncocytomas (P < .01). Claudin-8 was expressed in multiple patterns: In oncocytoma, 11 of 17 cases showed cytoplasmic, 4 of 17 membranous, and 2 of 17 negative reactions. In chromophobe renal cell carcinoma, 0 of 11 cases showed cytoplasmic, 3 of 11 membranous, and 8 of 11 negative reactions (P < .01). The immunohistochemical pattern of membranous claudin-7 and negative claudin-8 was seen in 7 of 11 chromophobe renal cell carcinomas and 1 of 17 oncocytomas (63% sensitivity, 84% specificity, 88% positive predictive value for chromophobe renal cell carcinoma). Negative claudin-7 and cytoplasmic claudin-8 were observed in 10 of 17 oncocytomas and 0 of 11 chromophobe renal cell carcinomas (59% sensitivity, 100% specificity and positive predictive value for oncocytoma). The distal nephron proteins claudin-7 and claudin-8 have potential use as immunohistochemical biomarkers in the differential diagnosis of chromophobe renal cell carcinoma and oncocytoma. Expression of claudin-7 and claudin-8 may reflect the relationship of chromophobe renal cell carcinoma and oncocytoma to intercalated cells of the cortical collecting duct. It may be necessary to identify additional biomarkers to include with claudin-7 and claudin-8 in a larger immunohistochemical panel to improve diagnostic sensitivity and specificity.
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PMID:Claudin-7 and claudin-8: immunohistochemical markers for the differential diagnosis of chromophobe renal cell carcinoma and renal oncocytoma. 1879 95

Claudin-7 knockout (CLDN7-/-) mice display renal salt wasting and dehydration phenotypes. To address the role of CLDN7 in kidneys, we established collecting duct (CD) cell lines from CLDN7+/+ and CLDN7-/- mouse kidneys. We found that deletion of CLDN7 increased the transepithelial resistance (TER) and decreased the paracellular permeability for Cl- and Na+ in CLDN7-/- CD cells. Inhibition of transcellular Cl- and Na+ channels has no significant effect on TER or dilution potentials. Current-voltage curves were linear in both CLDN7+/+ and CLDN7-/- CD cells, indicating that the ion flux was through the paracellular pathway. The impairment of Cl- and Na+ permeability phenotype can be rescued by CLDN7 re-expression. We also found that WNK4 (its mutations lead to hypertension) expression, but not WNK1, was significantly increased in CLDN7-/- CD cell lines as well as in primary CLDN7-/- CD cells, suggesting that the expression of WNK4 was modulated by CLDN7. In addition, deletion of CLDN7 upregulated the expression level of the apical epithelial sodium channel (ENaC), indicating a potential cross-talk between paracellular and transcellular transport systems. This study demonstrates that CLDN7 plays an important role in salt balance in renal CD cells and modulating WNK4 and ENaC expression levels that are vital in controlling salt-sensitive hypertension.
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PMID:Claudin-7 Modulates Cl- and Na+ Homeostasis and WNK4 Expression in Renal Collecting Duct Cells. 3138 27