Document Detail


Dragon enhances BMP signaling and increases transepithelial resistance in kidney epithelial cells.
MedLine Citation:
PMID:  20167703     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The neuronal adhesion protein Dragon acts as a bone morphogenetic protein (BMP) coreceptor that enhances BMP signaling. Given the importance of BMP signaling in nephrogenesis and its putative role in the response to injury in the adult kidney, we studied the localization and function of Dragon in the kidney. We observed that Dragon localized predominantly to the apical surfaces of tubular epithelial cells in the thick ascending limbs, distal convoluted tubules, and collecting ducts of mice. Dragon expression was weak in the proximal tubules and glomeruli. In mouse inner medullary collecting duct (mIMCD3) cells, Dragon generated BMP signals in a ligand-dependent manner, and BMP4 is the predominant endogenous ligand for the Dragon coreceptor. In mIMCD3 cells, BMP4 normally signaled through BMPRII, but Dragon enhanced its signaling through the BMP type II receptor ActRIIA. Dragon and BMP4 increased transepithelial resistance (TER) through the Smad1/5/8 pathway. In epithelial cells isolated from the proximal tubule and intercalated cells of collecting ducts, we observed coexpression of ActRIIA, Dragon, and BMP4 but not BMPRII. Taken together, these results suggest that Dragon may enhance BMP signaling in renal tubular epithelial cells and maintain normal renal physiology.
Authors:
Yin Xia; Jodie L Babitt; Richard Bouley; Ying Zhang; Nicolas Da Silva; Shanzhuo Chen; Zhenjie Zhuang; Tarek A Samad; Gary J Brenner; Jennifer L Anderson; Charles C Hong; Alan L Schneyer; Dennis Brown; Herbert Y Lin
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-02-18
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  21     ISSN:  1533-3450     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-01     Completed Date:  2010-04-22     Revised Date:  2011-07-27    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  666-77     Citation Subset:  IM    
Affiliation:
Center for Systems Biology, Program in Membrane Biology and Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Morphogenetic Proteins / physiology*
Cells, Cultured
Epithelial Cells / physiology*
Kidney
Mice
Nerve Tissue Proteins / physiology*
Neural Cell Adhesion Molecules / physiology*
Signal Transduction
Urothelium / cytology
Grant Support
ID/Acronym/Agency:
DK-42956/DK/NIDDK NIH HHS; K08 DK-075846/DK/NIDDK NIH HHS; K08 DK075846-04/DK/NIDDK NIH HHS; R01 DK-069533/DK/NIDDK NIH HHS; R01 DK-071837/DK/NIDDK NIH HHS; R03HD60641/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Bone Morphogenetic Proteins; 0/DRAGON protein, mouse; 0/Nerve Tissue Proteins; 0/Neural Cell Adhesion Molecules
Comments/Corrections

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