Spatio-temporal expression of the vascular endothelial growth factor (VEGF system and EG-VEGF in the thymus of dogs

Author(s)

Fernanda Rodrigues Agreste

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD)
• Defense date: 2010-07-08

Examining board members

Pedro Primo Bombonato; Hildebrando Gomes Benedicto; Kleber Gomes Franchini; Eduardo Mauricio Mendes de Lima; Arani Nanci Bomfim Mariana

• Advisor: Pedro Primo Bombonato

Abstract

The aim this study was therefore to evaluate the expression of growth factors responsible for the vasculogenic process throughout development and initial involution of the canine thymus. For that purpose, thymuses from fetuses (30, 40, 50 and 60 days), juvenile (6 months) and adult (1 year) dogs were collected. The tissues were examined stereologically and subjected to immunohistochemistry, Real Time PCR and western blot for components of the VEGF-system (VEGF-A, VEGF-C, Flt-1, KDR and Flt-4) and endocrine gland-derived (EG)-VEGF. By means of stereology, the total number of blood vessels increased during development and decreased during involution. These changes were statistically significant (p<0.05). All components of the VEGF-system and EG-VEGF were detected in all stages during development and involution. The corresponding proteins were localized in endothelial and epithelial cells of cortical and medullar regions, and EG-VEGF was detected only in epithelial cells of medular region. The VEGF-system and EG-VEGF protein and mRNA expression showed a specific time-dependent profile during development and involution. The VEGF system showed a constant expression during development and a progressive increase during involution, except KDR that showed increased during all development and involution and VEGF-C that showed high expression during involution. The EG-VEGF RNAm expression was increased during development and involution, but protein expression was high in early thymus development and decreased in involution, and remains constant during all period. Our results suggest that VEGF-system and EG-VEGF have similar biological activities in endocrine glands and different roles during thymus development and involution which have to be specified in further studies. Possible functions include a modulatory effect on thymic vasculogenesis and microenvironment, influencing thymocyte proliferation and differentiation, T-cell maturation, cell-cell interaction and thymic hormonal secretion. (AU)