Differentially expressed angiogenic genes in diabetic erectile tissue - Results from a microarray screening

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Angela Castela (Autor) Outra; Raquel Soares (Autor) FMUP; Fatima Rocha (Autor) Outra; Rui Medeiros (Autor) ICBAS; Ricardo Ribeiro (Autor) Outra; Catia Monteiro (Autor) Outra; Pedro Gomes (Autor) FMUP; Pedro Vendeira (Autor) Outra; Ronald Virag (Autor) Outra; Carla Costa (Autor) Outra

Revista

Título: Molecular Genetics and Metabolism

Vol. 105

Páginas: 255-262

ISSN: 1096-7192

Editora: Elsevier

Indexação

ISI Web of Knowledge - 14 Citações

Scopus - 16 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Outras ciências médicas

Outras Informações

ID Authenticus: P-002-DCP

DOI: 10.1016/j.ymgme.2011.11.002

Abstract (EN): 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 a-smooth muscle actin (alpha-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/ alpha-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.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8