First Author | Irsik DL | Year | 2018 |
Journal | Am J Physiol Renal Physiol | Volume | 315 |
Issue | 3 | Pages | F512-F520 |
PubMed ID | 29667912 | Mgi Jnum | J:279810 |
Mgi Id | MGI:6367842 | Doi | 10.1152/ajprenal.00231.2017 |
Citation | Irsik DL, et al. (2018) Renoprotective impact of estrogen receptor-alpha and its splice variants in female mice with type 1 diabetes. Am J Physiol Renal Physiol 315(3):F512-F520 |
abstractText | 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. |