| Item type: | Article | ||||||||||||||||||||||||||||||||||||||||
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| Journal or Publication Title: | The American journal of pathology | ||||||||||||||||||||||||||||||||||||||||
| Publisher: | Elsevier | ||||||||||||||||||||||||||||||||||||||||
| Volume: | 176 | ||||||||||||||||||||||||||||||||||||||||
| Number of Issue or Book Chapter: | 2 | ||||||||||||||||||||||||||||||||||||||||
| Page Range: | pp. 594-607 | ||||||||||||||||||||||||||||||||||||||||
| Date: | February 2010 | ||||||||||||||||||||||||||||||||||||||||
| Institutions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) | ||||||||||||||||||||||||||||||||||||||||
| Identification Number: |
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| Classification: |
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| Dewey Decimal Classification: | 500 Science > 500 Natural sciences & mathematics 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine | ||||||||||||||||||||||||||||||||||||||||
| Status: | Published | ||||||||||||||||||||||||||||||||||||||||
| Refereed: | Yes, this version has been refereed | ||||||||||||||||||||||||||||||||||||||||
| Created at the University of Regensburg: | No | ||||||||||||||||||||||||||||||||||||||||
| Item ID: | 30642 |
Abstract
In the kidney, hypoxia contributes to tubulointerstitial fibrosis, but little is known about its implications for glomerular damage and glomerulosclerosis. Chronic hypoxia was hypothesized to be involved in nephrosclerosis (NSC) or "hypertensive nephropathy." In the present study genome-wide expression data from microdissected glomeruli were studied to examine the role of hypoxia in ...
Abstract
In the kidney, hypoxia contributes to tubulointerstitial fibrosis, but little is known about its implications for glomerular damage and glomerulosclerosis. Chronic hypoxia was hypothesized to be involved in nephrosclerosis (NSC) or "hypertensive nephropathy." In the present study genome-wide expression data from microdissected glomeruli were studied to examine the role of hypoxia in glomerulosclerosis of human NSC. Functional annotation analysis revealed prominent regulation of hypoxia-associated biological processes in NSC, including angiogenesis, fibrosis, and inflammation. Glomerular expression levels of a majority of genes regulated by the hypoxia-inducible factors (HIFs) were significantly altered in NSC. Among these HIF targets, chemokine C-X-C motif receptor 4 (CXCR4) was prominently induced. Glomerular CXCR4 mRNA induction was confirmed by quantitative RT-PCR in an independent cohort with NSC but not in those with other glomerulopathies. By immunohistological analysis, CXCR4 showed enhanced positivity in podocytes in NSC biopsy specimens. This CXCR4 positivity was associated with nuclear localization of HIF1alpha only in podocytes of NSC, indicating transcriptional activity of HIF. As the CXCR4 ligand CXCL12/SDF-1 is constitutively expressed in podocytes, autocrine signaling may contribute to NSC. In addition, a blocking CXCR4 antibody caused significant inhibition of wound closure by podocytes in an in vitro scratch assay. These data support a role for CXCR4/CXCL12 in human NSC and indicate that hypoxia not only is involved in tubulointerstitial fibrosis but also contributes to glomerular damage in NSC.
Metadata last modified: 25 May 2018 13:15
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