کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3885357 1249510 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Darbepoetin alfa protects podocytes from apoptosis in vitro and in vivo
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
Darbepoetin alfa protects podocytes from apoptosis in vitro and in vivo
چکیده انگلیسی

Detachment or apoptosis of podocytes leads to proteinuria and glomerulosclerosis. There are no current interventions for diabetic or non-diabetic glomerular diseases specifically preventing podocyte apoptosis. Binding of erythropoiesis stimulating proteins (ESPs) to receptors on non-hematopoietic cells has been shown to have anti-apoptotic effects in vitro, in vivo, and in preliminary human studies. Recently, erythropoietin receptors were identified on podocytes; therefore, we tested effects of darbepoetin alfa in preventing podocyte apoptosis. Cultured immortalized mouse podocytes were treated with low-dose ultraviolet-C (uv-C) irradiation to induce apoptosis in the absence or presence of darbepoetin alfa. Apoptosis was quantified by Hoechst staining and by caspase 3 cleavage assessed by Western blots. Pretreatment with darbepoetin alfa significantly reduced podocyte apoptosis with this effect involving intact Janus family protein kinase-2 (JAK2) and AKT signaling pathways. Additionally, darbepoetin alfa was found protective against transforming growth factor-β1 but not puromycin aminonucleoside induced apoptosis. Mice with anti-glomerular antibody induced glomerulonephritis had significantly less proteinuria, glomerulosclerosis, and podocyte apoptosis when treated with darbepoetin alfa. Our studies show that treatment of progressive renal diseases characterized by podocyte apoptosis with ESPs may be beneficial in slowing progression of chronic kidney disease.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 72, Issue 4, 2 August 2007, Pages 489–498
نویسندگان
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