کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6164086 | 1249459 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Endothelin-converting enzyme is a plausible target gene for hypoxia-inducible factor
ترجمه فارسی عنوان
آنزیم تبدیل اندوتلین یک ژن هدف قابل قبول برای عامل القاء هیپوکسی است
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موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
چکیده انگلیسی
Renal endothelin-converting enzyme (ECE)-1 is induced in experimental diabetes and following radiocontrast administration, conditions characterized by renal hypoxia, hypoxia-inducible factor (HIF) stabilization, and enhanced endothelin synthesis. Here we tested whether ECE-1 might be a HIF-target gene in vitro and in vivo. ECE-1 transcription and expression increased in cultured vascular endothelial and proximal tubular cell lines, subject to hypoxia, to mimosine or cobalt chloride. These interventions are known to stabilize HIF signaling by inhibition of HIF-prolyl hydroxylases. In rats, HIF-prolyl-hydroxylase inhibition by mimosine or FG-4497 increased HIF-1α immunostaining in renal tubules, principally in distal nephron segments. This was associated with markedly enhanced ECE-1 protein expression, predominantly in the renal medulla. A progressive and dramatic increase in ECE-1 immunostaining over time, in parallel with enhanced HIF expression, was also noted in conditional von Hippel-Lindau knockout mice. Since HIF and STAT3 are cross-stimulated, we triggered HIF expression by STAT3 activation in mice, transfected by or injected with a chimeric IL-6/IL-6-receptor protein, and found a similar pattern of enhanced ECE-1 expression. Chromatin immunoprecipitation sequence (ChIP-seq) and PCR analysis in hypoxic endothelial cells identified HIF binding at the ECE-1 promoter and intron regions. Thus, our findings suggest that ECE-1 may be a novel HIF-target gene.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 87, Issue 4, April 2015, Pages 761-770
Journal: Kidney International - Volume 87, Issue 4, April 2015, Pages 761-770
نویسندگان
Mogher Khamaisi, Hala Toukan, Jonathan H. Axelrod, Christian Rosenberger, Galia Skarzinski, Ahuva Shina, Rina Meidan, Robert Koesters, Seymour Rosen, Gail Walkinshaw, Imari Mimura, Masaomi Nangaku, Samuel N. Heyman,