PMID- 29667912
OWN - NLM
STAT- MEDLINE
DCOM- 20190708
LR  - 20191121
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 315
IP  - 3
DP  - 2018 Sep 1
TI  - Renoprotective impact of estrogen receptor-alpha and its splice variants in female 
      mice with type 1 diabetes.
PG  - F512-F520
LID - 10.1152/ajprenal.00231.2017 [doi]
AB  - Estrogen has been implicated in the regulation of growth and immune function in 
      the kidney, which expresses the full-length estrogen receptor-alpha (ERalpha66), its ERalpha 
      splice variants, and estrogen receptor-beta (ERbeta). Thus, we hypothesized that these 
      splice variants may inhibit the glomerular enlargement that occurs early in type 
      1 diabetes (T1D). T1D was induced by streptozotocin (STZ) injection in 8- to 
      12-wk-old female mice lacking ERalpha66 (ERalpha66KO) or all ERalpha variants (alphaERKO), and 
      their wild-type (WT) littermates. Basal renal ERalpha36 protein expression was 
      reduced in the ERalpha66KO model and was downregulated by T1D in WT mice. T1D did not 
      alter ERalpha46 or ERbeta in WT-STZ; however, ERalpha46 was decreased modestly in ERalpha66KO 
      mice. Renal hypertrophy was evident in all diabetic mice. F4/80-positive 
      immunostaining was reduced in ERalpha66KO compared with WT and alphaERKO mice but was 
      higher in STZ than in Control mice across all genotypes. Glomerular area was 
      greater in WT and alphaERKO than in ERalpha66KO mice, with T1D-induced glomerular 
      enlargement apparent in WT-STZ and alphaERKO-STZ, but not in ERalpha66KO-STZ mice. 
      Proteinuria and hyperfiltration were evident in ERalpha66KO-STZ and alphaERKO-STZ, but 
      not in WT-STZ mice. These data indicate that ERalpha splice variants may exert an 
      inhibitory influence on glomerular enlargement and macrophage infiltration during 
      T1D; however, effects of splice variants are masked in the presence of the 
      full-length ERalpha66, suggesting that ERalpha66 acts in opposition to its splice 
      variants to influence these parameters. In contrast, hyperfiltration and 
      proteinuria in T1D are attenuated via an ERalpha66-dependent mechanism that is 
      unaffected by splice variant status.
FAU - Irsik, Debra L
AU  - Irsik DL
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center , Omaha, Nebraska.
FAU - Romero-Aleshire, Melissa J
AU  - Romero-Aleshire MJ
AD  - Department of Physiology, University of Arizona , Tucson, Arizona.
FAU - Chavez, Erin M
AU  - Chavez EM
AD  - Department of Physiology, University of Arizona , Tucson, Arizona.
FAU - Fallet, Rachel W
AU  - Fallet RW
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center , Omaha, Nebraska.
FAU - Brooks, Heddwen L
AU  - Brooks HL
AD  - Department of Physiology, University of Arizona , Tucson, Arizona.
FAU - Carmines, Pamela K
AU  - Carmines PK
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center , Omaha, Nebraska.
FAU - Lane, Pascale H
AU  - Lane PH
AD  - Department of Cellular and Integrative Physiology, University of Nebraska Medical 
      Center , Omaha, Nebraska.
AD  - Department of Pediatrics, University of Oklahoma Health Sciences Center , 
      Oklahoma City, Oklahoma.
LA  - eng
GR  - R01 HL131834/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180418
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Blood Glucose)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Protein Isoforms)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Blood Glucose/metabolism
MH  - Diabetes Mellitus, Experimental/chemically induced/genetics/*metabolism
MH  - Diabetes Mellitus, Type 1/chemically induced/genetics/*metabolism
MH  - Diabetic Nephropathies/chemically induced/genetics/metabolism/*prevention & 
      control
MH  - Estrogen Receptor alpha/deficiency/genetics/*metabolism
MH  - Female
MH  - Glomerular Filtration Rate
MH  - Kidney Glomerulus/*metabolism/pathology/physiopathology
MH  - Macrophages/metabolism
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Protein Isoforms
MH  - Proteinuria/genetics/metabolism/prevention & control
MH  - Streptozocin
MH  - Weight Gain
PMC - PMC6842867
OTO - NOTNLM
OT  - estrogen receptors
OT  - glomeruli
OT  - macrophage
OT  - type 1 diabetes
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2018/04/19 06:00
MHDA- 2019/07/10 06:00
PMCR- 2019/09/01
CRDT- 2018/04/19 06:00
PHST- 2018/04/19 06:00 [pubmed]
PHST- 2019/07/10 06:00 [medline]
PHST- 2018/04/19 06:00 [entrez]
PHST- 2019/09/01 00:00 [pmc-release]
AID - F-00231-2017 [pii]
AID - 10.1152/ajprenal.00231.2017 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2018 Sep 1;315(3):F512-F520. doi: 
      10.1152/ajprenal.00231.2017. Epub 2018 Apr 18.