足细胞
细胞凋亡
雌激素受体
生物
免疫印迹
雌激素受体
膜联蛋白
雌激素受体α
内科学
内分泌学
流式细胞术
分子生物学
肾
医学
基因
蛋白尿
生物化学
癌症
乳腺癌
作者
Sebastian Kummer,Stefanie Jeruschke,Lara Vanessa Wegerich,Andrea Peters,Petra Lehmann,Annette Seibt,Friederike Mueller,Nadezda Koleganova,Elisabeth Halbenz,Claus Peter Schmitt,Markus Bettendorf,Ertan Mayatepek,Marie-Luise Groß-Weißmann,Jun Oh
出处
期刊:PLOS ONE
[Public Library of Science]
日期:2011-11-11
卷期号:6 (11): e27457-e27457
被引量:44
标识
DOI:10.1371/journal.pone.0027457
摘要
Epidemiological studies have demonstrated that women have a significantly better prognosis in chronic renal diseases compared to men. This suggests critical influences of gender hormones on glomerular structure and function. We examined potential direct protective effects of estradiol on podocytes.Expression of estrogen receptor alpha (ERα) was examined in podocytes in vitro and in vivo. Receptor localization was shown using Western blot of separated nuclear and cytoplasmatic protein fractions. Podocytes were treated with Puromycin aminonucleoside (PAN, apoptosis induction), estradiol, or both in combination. Apoptotic cells were detected with Hoechst nuclear staining and Annexin-FITC flow cytometry. To visualize mitochondrial membrane potential depolarization as an indicator for apoptosis, cells were stained with tetramethyl rhodamine methylester (TMRM). Estradiol-induced phosphorylation of ERK1/2 and p38 MAPK was examined by Western blot. Glomeruli of ERα knock-out mice and wild-type controls were analysed by histomorphometry and immunohistochemistry.ERα was consistently expressed in human and murine podocytes. Estradiol stimulated ERα protein expression, reduced PAN-induced apoptosis in vitro by 26.5±24.6% or 56.6±5.9% (flow cytometry or Hoechst-staining, respectively; both p<0.05), and restored PAN-induced mitochondrial membrane potential depolarization. Estradiol enhanced ERK1/2 phosphorylation. In ERα knockout mice, podocyte number was reduced compared to controls (female/male: 80/86 vs. 132/135 podocytes per glomerulus, p<0.05). Podocyte volume was enhanced in ERα knockout mice (female/male: 429/371 µm(3) vs. 264/223 µm(3) in controls, p<0.05). Tgfβ1 and collagen type IV expression were increased in knockout mice, indicating glomerular damage.Podocytes express ERα, whose activation leads to a significant protection against experimentally induced apoptosis. Possible underlying mechanisms include stabilization of mitochondrial membrane potential and activation of MAPK signalling. Characteristic morphological changes indicating glomerulopathy in ERα knock-out mice support the in vivo relevance of the ERα for podocyte viability and function. Thus, our findings provide a novel model for the protective influence of female gender on chronic glomerular diseases.
科研通智能强力驱动
Strongly Powered by AbleSci AI