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Endothelin B (ETB) receptor protects against endoplasmic reticulum (ER) stress‐induced renal damage
Author(s) -
De Miguel Carmen,
Hobbs Janet L,
Pollock David M,
Pollock Jennifer S
Publication year - 2013
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.27.1_supplement.906.5
Subject(s) - endocrinology , medicine , renal cortex , endoplasmic reticulum , unfolded protein response , chemistry , endothelin 1 , endothelin receptor , kidney , receptor , biology , biochemistry
Tunicamycin (TM) blocks glycoprotein synthesis, leading to endoplasmic reticulum (ER) stress and tissue damage. Endothelin (ET1) via ET A and ET B receptors is implicated in renal injury. We hypothesized that ET B deficient rats ( sl/sl ) develop exaggerated renal ER stress and/or inflammation compared to wild type (wt) rats in response to acute TM treatment. Wt and sl/sl rats (n=3–5) were treated with TM (2μg/g bwt; i.p.) or vehicle; kidneys, plasma and urine were collected 24h later. ER stress markers and cytokines were determined by qRT‐PCR in renal cortex, outer and inner medulla. Plasma, urine ET1 and renal inflammatory cell infiltration were assessed by ELISA and histology. Sl/sl rats showed enhanced sensitivity to TM by increased expression of GRP78 in inner medulla (wt vs. sl/sl , fold change: 1.52±0.31 vs. 4.60±0.32) and outer medulla (153.6±57.3 vs. 3413±625.8), CHOP in inner medulla (1.46±0.63 vs. 25.50±2.6) and cortex (0.34±0.08 vs. 12.08±2.77), and spliced XBP‐1 in outer medulla (0.91±0.61 vs. 15.71±1.92) and cortex (0.28±0.03 vs. 7.96±1.84). TM did not increase plasma ET1 or urinary ET1 excretion in either rat genotype. Renal CCL2 and IL‐6 expression, as well as macrophage and T‐cell infiltration, were similar between both genotypes in response to TM. Induction of renal ER stress genes is significantly greater in sl/sl rats, thus ET B receptors may be protective against ER stress‐induced renal damage.