کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3296325 | 1209867 | 2007 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
STAT3 Is Required for IL-6-gp130-Dependent Activation of Hepcidin In Vivo
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای گوارشی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Background & Aims: Hepcidin is a peptide hormone that is central to the regulation of iron homeostasis. In response to interleukin 6 (IL-6), hepatocytes produce hepcidin that decreases iron release/transfer from enterocytes and macrophages and causes hypoferremia. To clarify the molecular pathways involved in hepcidin activation by IL-6, we used different mice strains in which the main IL-6/gp130 signaling pathways have been genetically disrupted. Methods: We generated mice with hepatocyte-specific deletion of the IL-6 signal-transducing gp130 receptor (alfpgp130 LoxP/LoxP), with a gp130 receptor lacking the essential region for STAT1 and -3 activation (alfpCre gp130ÎSTAT/LoxP) or mice expressing a gp130 allele lacking the essential tyrosine for RAS-MAPK activation (alfpCregp130Y757F/LoxP). We studied gp130-dependent pathways and hepcidin mRNA expression by Western blot, reverse-transcription polymerase chain reaction, and Northern blot in vivo and ex vivo. Results: IL-6 stimulated phospho STAT3, serum amyloid A (SAA), and suppressor of cytokine signaling 3 (SOCS3) expression in livers of wild-type and alfpCregp130Y757F/LoxP mice, whereas this response was blocked in alfpCre gp130LoxP/LoxP and alfpCre gp130ÎSTAT/LoxP mice. In wild-type and alfpCregp130Y757F/LoxP animals, significantly higher hepcidin mRNA expression was found 3 to 6 hours after IL-6 stimulation. In contrast, no IL-6-dependent regulation of hepcidin mRNA expression was found in alfpgp130 ÎSTAT/LoxP and AlfpCre gp130 LoxP/LoxP animals. In primary hepatocytes, higher hepcidin mRNA expression after IL-6 stimulation was only observed when gp130-STAT3-dependent signaling was intact. Conclusions: We have demonstrated that both in vivo and in vitro STAT3 is the key transcription factor responsible for IL-6 activation of hepcidin gene expression in the liver.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Gastroenterology - Volume 132, Issue 1, January 2007, Pages 294-300
Journal: Gastroenterology - Volume 132, Issue 1, January 2007, Pages 294-300
نویسندگان
Antonello Pietrangelo, Uta Dierssen, Linda Valli, Cinzia Garuti, Agrani Rump, Elena Corradini, Matthias Ernst, Christian Klein, Christian Trautwein,