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)

Antibody microarray technology identified Nup88 (nucleoporin 88) as a highly up-regulated protein in response to osmotic stress in inner medullary collecting duct (IMCD3) cells. Changes in expression were verified by Western blot and quantitative PCR for protein and message expression. In mouse and human kidney, Nup88 expression was substantial in the papilla, whereas it was nearly absent in the cortex. Furthermore, the expression of Nup88 increased 410.4 +/- 22% in the papilla of mice after 36 h of thirsting. Nup88 protein expression in IMCD3 cells was significantly up-regulated in the first 8 h following exposure to acute osmotic stress, indicating that Nup88 is an early response protein. To define the function of Nup88 in the osmotic stress response, the transcription factor associated with hypertonicity, tonicity enhancer-binding protein (TonEBP), was cloned upstream of the green fluorescent protein. Employing this construct, we demonstrate that silencing Nup88 in IMCD3 cells acutely stressed to hypertonic conditions reduces nuclear retention of TonEBP, resulting in a substantial blunting in transcription of important osmotic stress response target genes and reduced cell viability. Finally, we show that in IMCD3 cells, nuclear export of TonEBP under isotonic conditions involves CRM-1 but under hypertonic stress is CRM1-independent. Our data, therefore, suggest that Nup88 is up-regulated in response to hypertonic stress and acts to retain TonEBP in the nucleus, activating transcription of critical osmoprotective genes.
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PMID:Nucleoporin 88 (Nup88) is regulated by hypertonic stress in kidney cells to retain the transcription factor tonicity enhancer-binding protein (TonEBP) in the nucleus. 1860 15

The hypertonic inner medulla poses challenges to the cells that inhabit this area of the nephron. We employed discovery tools including proteomics and genomics to identify proteins that subserve the adaptive response. The gamma subunit of the Na/K-ATPase is critical to the survival of cells in hypertonic conditions, as silencing it increases osmosensitvity, and overexpression increases osmotolerance. The inner medullary collecting duct (IMCD) has high transepithelial resistance (TER). Proteins responsible for tight junction integrity are upregulated in hypertonic states. Multi PDZ protein 1 (MUPP1), a PDZ scaffolding protein, targets Claudin 4 to the tight junction. The silencing of either of these proteins decreases TER and renders the epithelium leaky. The accumulation of inert osmolytes is integral to the adaptive response. The genes involved are regulated by the transcription factor Tonicity Enhancer Binding Protein. An osmoregulated nuclear protein Nup88 is critical to the retention of this transcription factor in the nucleus and to the generation of the osmolytes. In summary, IMCD cells bring forth a coordinated response to hypertoncity that is necessary for cell survival and function of these cells in anisotonic conditions.
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PMID:How do kidney cells adapt to survive in hypertonic inner medulla? 1976 91