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ERα66 contributes to early diabetic renal disease in mice
Author(s) -
Irsik Debra Lima,
Fallet Rachel W.,
Adun Ese,
Chavez Erin,
Brooks Heddwen L.,
Carmines Pamela K.,
Lane Pascale H.
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.702.12
Subject(s) - medicine , endocrinology , streptozotocin , renal cortex , estrogen receptor , renal function , estrogen receptor alpha , kidney , diabetic nephropathy , diabetes mellitus , chemistry , cancer , breast cancer
Estrogen influences the development of type 1 diabetes (T1D), but its role in diabetic renal disease is unknown. Because the kidney expresses the full‐length estrogen receptor (ERα66), its ERα36 splice variant, and ERβ, we hypothesized that ER protein levels impact renal structure and function during T1D. T1D was induced by streptozotocin (STZ) injection in 8‐wk‐old C57/Bl6 mice that are null for ERα66 but still express ERα splice variants (ERα66KO) and their wild‐type (WT) littermates. Nondiabetic (sham) mice received STZ vehicle injection. Six weeks later, glomerular area was greater in STZ‐WT (3285±223 μm 2 ) than in sham‐WT (2212±96 μm 2 ; P <0.05), but did not differ between sham‐ and STZ‐ERα66KO (2386±91 and 2378±62 μm 2 , respectively). Renal F4/80 + staining was greater in STZ‐WT than in sham‐WT (0.76±0.08 vs 0.32±0.09 AU/area; P <0.05), and did not differ between sham‐ and STZ‐ERα66KO. Renal cortical ERα36 protein levels in STZ‐WT averaged 66% of sham‐WT ( P < 0.05), but did not differ between Sham‐ and STZ‐ERα66KO. Renal ERβ levels were similar in all groups. Phosphorylated‐to‐total ERK1/2 was increased 2.5‐fold in the renal cortex of STZ‐treated mice regardless of genotype ( P < 0.05). Thus, although ERα is not implicated in the T1D‐induced renal cortical ERK activation, ERα66KO protects against the glomerular enlargement (an early marker of nephropathy) and renal macrophage infiltration accompanying T1D.