Leprosy patients: neurotrophic factors and axonal markers in skin lesions / Pacientes com hanseníase: fatores neurotróficos e marcadores axonais em lesões de pele

Neurotrophins are growth factors with crucial roles in neural pathophysiology. These mediators functionally modulate nociceptive fibers, and changes in neurotrophins expression have been correlated with early loss of nociception in leprosy. This study investigated the expression of NGF, BDNF, and NT3 in dermal nerves of leprosy patients. Characterization of Remak bundles was achieved by p75NTR, and axonal markers NF-L and PGP 9.5 immunostaining. Clinical parameters of neural impairment have been evaluated by Semmes-Wenstein monofilaments. Our findings demonstrated decrease of NGF in borderline leprosy, when compared to control specimens. Similar results were observed in PGP 9.5 expression (borderline: p<0.001 and lepromatous: p<0.05) and NF-L (lepromatous: p<0.05), suggesting advanced Remak bundles degeneration in multibacillary leprosy. It has also been observed positive correlation between p75NTR and PGP 9.5, indicating association between Schwann cells and axons in Remak bundles. Present data indicate that neurotrophins imbalance may participate in the establishment of peripheral nerve damage.

Neurotrofinas são fatores de crescimento com papel fundamental na fisiopatologia neural. Esses mediadores modulam funcionalmente fibras nociceptivas. Mudanças em sua expressão têm sido relacionadas à perda precoce da nocicepção na hanseníase. Este estudo investigou a expressão de NGF, BDNF e NT3 em nervos dérmicos de pacientes hansenianos. A caracterização de fibras nervosas não mielinizadas foi feita por p75NTR e marcadores axonais NF-L e PGP 9.5. Os parâmetros clínicos de dano neural foram avaliados por monofilamentos Semmes-Wenstein. Nossos achados demonstram diminuição de NGF nos pacientes dimorfos em comparação aos controles. Resultados similares foram observados para PGP 9.5 (dimorfos: p<0,001; virchowianos: p<0,05) e NF-L (virchowianos: p<0.05), sugerindo degeneração avançada das terminações nervosas na hanseníase multibacilar. Foi observada correlação positiva entre p75NTR e PGP 9.5, indicando associação entre células de Schwann e axônios em fibras nervosas não mielinizadas. Os resultados indicam que o desequilíbrio na expressão das neurotrofinas pode participar do dano neural periférico.

Importancia del factor de crecimiento nervioso (NGF) en la función normal del ovario y en el cáncer ovárico epitelial / Importance of the factor of nerve growth (NGF) in the normal function of the ovary and in the epithelial ovarian cancer

En el ovario normal, la angiogénesis es un proceso finalmente regulado y es fundamental para la función ovárica (esteroidogénesis y ovulación). En el cáncer ovárico epitelial, la angiogénesis se encuentra aumentada y uno de los elementos angiogénicos más importantes en ambos casos es el factor de crecimiento del endotelio vascular (VEGF). Por otra parte, el factor de crecimiento nervioso (NGF), también ha sido considerado un factor angiogénico tanto directo como indirecto a través del aumento de VEGF en tejidos no-neuronales, diferentes del ovario. Antecedentes demuestran la expresión de NGF en ovario de mamíferos, incluyendo el ovario humano. Nuestro objetivo fue examinar la relación entre NGF y VEGF en ovario normal y cáncer ovárico epitelial. Nuestros resultados demuestran que en ovario normal, NGF y su receptor específico (trkA), se expresan en células de la granulosa de folículos pre-antrales y antrales, similar a lo descrito para VEGF. Además, NGF aumenta la expresión de VEGF en células de granulosa humana en cultivo. En cáncer ovárico epitelial, NGF y trkA se sobre-expresan en células epiteliales y NGF al activar a su receptor trkA, aumenta la expresión de VEGF en cultivo de explantes de este tejido. Estos resultados demuestran que NGF y trkA podrían estar involucrados a través de la regulación de la expresión VEGF, en la angiogénesis del ovario normal como en cáncer ovárico epitelial.

In the normal ovary, the angiogenesis is a fundamental and cyclical process that happens in each ovulation. In the epithelial ovarian cancer, the angiogenesis is increased and as it is known, it is essential for the growth of solid tumors. The endothelial growth factor (VEGF) is one of the most important factors in this process. The nerve growth factor (NGF), has been considered as a direct and indirect angiogenic factor through the increase of VEGF expression in non-neuronal tissues, different from the ovary Previous reports have demonstrated NGF expression in mammals ovary, including the human ovary. Our aim was to examine the relation between NGF and VEGF in normal ovary and epithelial ovarian cancer. Our finding demonstrated that in normal ovary, NGF and its specific receptor (trkA) are expressed in granulosa cells from pre-antrals and antrals follicles, similar to those reported for VEGF. In addition, NGF increases the VEGF expression in human granulosa cells in culture. NGF and trkA are over-expressed in epithelial cells and NGF activates its trkA receptor, increasing VEGF expression in cultured explants of epithelial ovarian cancer. These results show that NGF and trkA could be involved in angiogenesis process in normal ovary and epihelial ovarian cancer.