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Expression of GRP78 is increased by vasopressin in the mouse renal medulla
Author(s) -
Cai Qi,
McReynolds Matthew R,
Keck Maggie,
TaylorGarcia Katherine M,
Brooks Heddwen L
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1220-b
Subject(s) - aquaporin 2 , medicine , renal medulla , endocrinology , vasopressin , kidney , biology , aquaporin 1 , osmotic concentration , medulla , gene expression , gene , biochemistry , water channel , inlet , mechanical engineering , engineering
To identify vasopressin regulated genes in the renal medulla, we infused dDAVP, a V2 receptor agonist, for 7 days via osmotic mini‐pump, into both wild type and AQP1 KO mice. Following dDAVP infusion in wild type mice urine osmolarity increased to 2847 ± 87mOsm vs control 1644 ±190mOsm. In AQP1KO mice, dDAVP infusion caused a small but significant increase in urine osmolarity; 893 ± 62mOsm vs control KO 581 ± 26mOsm. Changes in medullary gene expression were identified via microarray analysis. GRP78 mRNA was identified as increasing in the renal medulla of both sets of animals following dDAVP infusion. GRP78 is an ER stress protein known to be regulated by malfolded proteins and ER Ca ++ depletion. Protein abundance of GRP78 was significantly increased by dDAVP; 206% ± 14 in wild type dDAVP; 148% ± 4 in AQP1 KO dDAVP. We localized the expression of GRP78 protein using immunohistochemistry. GRP78 was expressed in collecting duct cells and co‐localized with AQP2 protein expression. In AQP1KO mice GRP78 protein was induced by dDAVP infusion mainly in the tip of renal inner medulla. The expression of renal aquaporins was differentially altered between wild type and AQP1 KO animals following dDAVP infusion. In dDAVP infused wild type mice AQP2 protein increased by 149% ± 15; AQP3 by 354% ± 21; AQP4 by 850% ±26. In dDAVP infused AQP1KO mice AQP2, 3 protein were unchanged, AQP4 was increased, 190% ± 20. GRP78 regulation via vasopressin was investigated in cultured mIMCD3 cells; GRP78 protein expression was significantly increased after 8 hours of 10 −8 M dDAVP. These data suggest that V2 receptor activation increases the expression of GRP78 in renal medullary collecting duct cells.