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)

Collecting duct-derived ET-1 regulates salt excretion and blood pressure. We have reported the presence of an inner medullary collecting duct (IMCD)-specific enhancer region in the 5'-upstream ET-1 promoter (Strait, K. A., Stricklett, P. K., Kohan, J. L., Miller, M. B., and Kohan, D. E. (2007) Am. J. Physiol. Renal Physiol. 293, F601-F606). The current studies provide further characterization of the ET-1 5'-upstream distal promoter to identify the IMCD-specific enhancer elements. Deletion studies identified two regions of the 5'-upstream ET-1 promoter, -1725 to -1319 bp and -1319 to -1026 bp, which were required for maximal promoter activity in transfected rat IMCD cells. Transcription factor binding site analysis of these regions identified two consensus nuclear factor of activated T-cells (NFAT) binding sites at -1263 and -1563. EMSA analysis using nuclear extracts from IMCD cells showed that both the -1263 and the -1563 NFAT sites in the ET-1 distal promoter competed for NFAT binding to previously identified NFAT sites in the IL-2 and TNF genes. Gel supershift analysis showed that each of the NFAT binding sites in the ET-1 promoter bound NFAT proteins derived from IMCD nuclear extracts, but they selectively bound different NFAT isoforms; ET-1263 bound NFATc1, whereas ET-1563 bound NFATc3. Site-directed mutagenesis of either the ET-1263 or the ET-1563 sites prevented NFAT binding and reduced ET-1 promoter activity. Thus, NFAT appears to be an important regulator of ET-1 transcription in IMCD cells, and thus, it may play a role in controlling blood pressure through ET-1 regulation of renal salt excretion.
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PMID:Identification of two nuclear factor of activated T-cells (NFAT)-response elements in the 5'-upstream regulatory region of the ET-1 promoter. 2064 10

Transcription factor GATA binding protein 3 (GATA3) has been suggested as a marker of urothelial carcinoma of the bladder and upper urinary tract. Its expression in primary and metastatic renal tumors has not been fully determined. We evaluated GATA3 expression in 47 oncocytomas, 196 primary renal cell carcinomas (RCCs) (71 clear cell, 53 papillary, 21 Xp11.2, 33 chromophobe RCCs, and 18 collecting duct carcinomas [CDC]), and 43 unrelated metastatic RCCs (41 clear cell and 2 Xp11.2 RCC). GATA3 nuclear expression was evaluated in tissue microarrays built from archival tissues using immunohistochemistry. Intensity (0 to 3+) and extent (percentage) of expression were assessed. Several cutoff values (>0%, >5%, and >10%) were evaluated to indicate GATA3 positivity. Among oncocytomas, 9 (19%) of 47 had some degree of nuclear GATA3 expression with median extent of 0% (0%-100%). When using either 5% or 10% cutoff values, 5 (11%) of 47 oncocytomas were positive. In primary RCCs, 6 (3%) of 196 had some degree of nuclear expression with a median extent of 0% (0%-100%). When using either 5% or 10% cutoff values, 2 cases remained positive (1%) (Xp11.2 and CDC). All metastatic RCCs were negative. We found an overall lack of GATA3 expression in primary and metastatic RCCs. GATA3 is expressed in a minority of oncocytomas, Xp11.2-RCC, and CDC. Given GATA3 positivity in upper urinary tract urothelial carcinoma, our findings support a role for GATA3 in the differential diagnosis of primary renal masses and a utility in the interrogation of metastatic tumors of unknown primary in the presence of a renal mass.
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PMID:Comprehensive profile of GATA binding protein 3 immunohistochemical expression in primary and metastatic renal neoplasms. 2431 6