| Pre-ischemic Targeting of HIF Prolyl Hydroxylation Inhibits Fibrosis associated with Acute Kidney Injury. | |
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MedLine Citation:
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PMID: 22262480 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Acute kidney injury (AKI) due to ischemia is an important contributor to the progression of chronic kidney disease (CKD). Key mediators of cellular adaptation to hypoxia are oxygen-sensitive hypoxia-inducible factors (HIF), which are regulated by prolyl-4-hydroxylase domain (PHD)-containing dioxygenases. While activation of HIF protects from ischemic cell death, HIF has been shown to promote fibrosis in experimental models of CKD. The impact of HIF activation on AKI-induced fibrosis has not been defined. Here we investigated the impact of pharmacologic HIF activation on AKI-associated fibrosis and inflammation. We found that pharmacologic inhibition of HIF prolyl hydroxylation prior to AKI ameliorated fibrosis and prevented anemia, while inhibition of HIF prolyl hydroxylation in the early recovery phase of AKI did not affect short- or long-term clinical outcome. Therefore, pre-ischemic targeting of the PHD/HIF pathway represents an effective therapeutic strategy for the prevention of CKD resulting from AKI, and warrants further investigation in clinical trials. |
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Authors:
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Pinelopi P Kapitsinou; Jonathan Jaffe; Mark Michael; Christina E Swan; Kevin J Duffy; Connie L Erickson-Miller; Volker Hans Haase |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-18 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: - ISSN: 1522-1466 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Vanderbilt University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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