| First Author | Kummer S | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 11 | Pages | e27457 |
| PubMed ID | 22096576 | Mgi Jnum | J:180970 |
| Mgi Id | MGI:5308487 | Doi | 10.1371/journal.pone.0027457 |
| Citation | Kummer S, et al. (2011) Estrogen receptor alpha expression in podocytes mediates protection against apoptosis in-vitro and in-vivo. PLoS One 6(11):e27457 |
| abstractText | CONTEXT/OBJECTIVE: 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. METHODS: Expression of estrogen receptor alpha (ERalpha) 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 ERalpha knock-out mice and wild-type controls were analysed by histomorphometry and immunohistochemistry. RESULTS: ERalpha was consistently expressed in human and murine podocytes. Estradiol stimulated ERalpha 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 ERalpha 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 ERalpha knockout mice (female/male: 429/371 microm(3) vs. 264/223 microm(3) in controls, p<0.05). Tgfbeta1 and collagen type IV expression were increased in knockout mice, indicating glomerular damage. CONCLUSIONS: Podocytes express ERalpha, 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 ERalpha knock-out mice support the in vivo relevance of the ERalpha for podocyte viability and function. Thus, our findings provide a novel model for the protective influence of female gender on chronic glomerular diseases. |
