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The full‐length estrogen receptor ERα66 mediates ERK activation and downregulation of ERα36 and ERβ expression in kidneys of female diabetic mice
Author(s) -
Irsik Debra Lima,
Fallet Rachel W.,
Carmines Pamela K.,
Lane Pascale H.
Publication year - 2012
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.26.1_supplement.1096.9
Subject(s) - endocrinology , medicine , downregulation and upregulation , estrogen receptor , diabetes mellitus , streptozotocin , diabetic nephropathy , kidney , western blot , estrogen receptor alpha , type 2 diabetes , estrogen , receptor , estrogen receptor beta , chemistry , biochemistry , cancer , breast cancer , gene
The kidney expresses multiple estrogen receptors, including the full‐length ERα66, its ERα36 splice variant, and ERβ. We previously reported that female ERα66KO mice (which lack a functional ERα66, but still express ERα36) were protected from diabetes‐induced glomerular enlargement, an early marker of renal complications. We hypothesized that diabetes triggers ER‐dependent pro‐hypertrophic signaling events, in concert with altered ER protein levels. Kidneys were harvested 2 wks after inducing type 1 diabetes (streptozotocin injection) in female wild‐type (WT) and ERα66KO mice, with insulin provided to temper the degree of hyperglycemia; sham mice received vehicle treatments. Western blot analysis revealed that phosphorylated‐to‐total ERK1/2 was increased in kidneys from diabetic WT mice, averaging 170±34 % of sham WT ( P <0.05); however, this parameter was unaltered by diabetes in ERα66KO mice (97±13 % of sham ERα66KO). Renal ERα36 and ERβ protein levels were reduced in diabetic WT mice, averaging 42±7 and 43±5 % of sham WT values, respectively (both P < 0.05). In contrast, diabetes did not significantly decrease renal ERα36 and ERβ levels in ERα66KO mice. In summary, the renal ERα66‐dependent events triggered by diabetes include downregulation of both ERα36 and ERβ, as well as ERK activation. These processes may contribute to the glomerular enlargement that arises early in diabetes.