کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3897531 1250260 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Hypoxia-Inducible Transcription Factors and Their Role in Renal Disease
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیماری‌های کلیوی
پیش نمایش صفحه اول مقاله
Hypoxia-Inducible Transcription Factors and Their Role in Renal Disease
چکیده انگلیسی
The 2 hypoxia inducible factors (HIF)-1α and HIF-2α are key mediators of cellular adaptation to hypoxia. They show a specific distribution pattern and possibly have complementary transcriptional targets in the kidney: HIF-1α is found mainly in tubular and HIF-2α in peritubular interstitial, endothelial, and glomerular cells. Both isoforms are regulated by oxygen-dependent hydroxylation of specific amino acid residues, which determines protein stability and transcriptional activity. Small molecule inhibitors of HIF hydroxylases act as pharmacologic inducers of HIF. HIF target genes are involved in cellular mechanisms that increase hypoxia tolerance or improve oxygen supply at the systemic or regional level, but also have been implicated in cellular apoptosis and profibrotic mechanisms. In experimental acute kidney injury the up-regulation of HIF either through endogenous hypoxia-sensing or after pharmacologic HIF stabilization confers tissue protection. Thus, HIF stabilization offers a promising novel and clinically feasible approach for nephroprotection. On the other hand, continuous activation of the HIF system occurs in kidney cancer and potentially promotes tumor growth. HIF therefore also is explored as a target for anticancer therapy.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Seminars in Nephrology - Volume 27, Issue 3, May 2007, Pages 363-372
نویسندگان
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