| Differentially expressed angiogenic genes in diabetic erectile tissue - Results from a microarray screening. | |
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MedLine Citation:
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PMID: 22133301 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Diabetes-induced metabolic derangements promote endothelial malfunction, contributing to erectile dysfunction (ED). However, it remains unclear which angiogenic molecular mechanisms are deregulated in diabetic corpus cavernosum (CC). We investigated early and late alterations in cavernosal angiogenic gene expression associated to diabetes. Angiogenic changes were assessed in penile tissue of streptozotocin-induced Wistar rats, in an early (2-week) and established stage (8-week) of diabetes. Differentially expressed genes were identified by microarrays and expression data validated by quantitative real-time PCR (qrt-PCR). At protein level, quantitative immunohistochemistry confirmed the arrays data and dual immunofluorescence for selected alterations and α-smooth muscle actin (α-SMA) identified the cellular location of target proteins. The selected differentially expressed genes were also evaluated in human non-diabetic and diabetic CC by quantitative immunolabeling. At 2-week diabetes there was no differential gene expression between non-diabetic and diabetic CC. At 8-week, 10 genes were found down-regulated in diabetics. The results were validated by qrt-PCR for the insulin-like growth factor-1 (Igf1) and the natriuretic peptide receptor-1 (Npr1) genes. Dual immunofluorescence for IGF-1/ α-SMA showed predominant localization of IGF-1 in SM. NPR-1 expression was diffuse and mostly present in trabecular fibroblasts and SM. Quantitative immunostaining confirmed the decreased expression of both proteins in diabetic tissues. Concordantly, we detected a significant reduction in IGF-1 and NPR-1 protein expressions in human diabetic samples. Microarray analysis identified 10 angiogenic-related molecules deregulated in CC of established diabetes. Among them, IGF-1 and NPR-1 were significantly down-regulated and might result in preventive/therapeutic targets for ED management. |
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Authors:
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Angela Castela; Raquel Soares; Fátima Rocha; Rui Medeiros; Ricardo Ribeiro; Cátia Monteiro; Pedro Gomes; Pedro Vendeira; Ronald Virag; Carla Costa |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-10 |
Journal Detail:
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Title: Molecular genetics and metabolism Volume: - ISSN: 1096-7206 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-12-2 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9805456 Medline TA: Mol Genet Metab Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Institute for Molecular and Cell Biology of the University of Porto (IBMC-UP), Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; Department of Biochemistry (U38-FCT), Faculty of Medicine of the University of Porto, Alameda Prof. Hernani Monteiro, 4200-319 Porto, Portugal. |
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