Estudo do Fator de Inibição da Migração de Macrófagos (MIF) no Desenvolvimento do Lobo Dorsal da Próstata de Camundongos

Abstract

The prostate is a gland attached to the male genital system of mammals that undergoes an important period of postnatal development. The activation of signaling pathways related to cell proliferation and death are essential for prostate development. In turn, macrophage migration inhibitory factor (MIF) was identified almost six decades ago as a pro-inflammatory cytokine. Subsequent studies gradually elucidated its indispensability for the performance of numerous other cellular functions, such as the triggering of signaling pathways, such as the previously mentioned pathways, which promote the expression of anti-apoptotic, pro-proliferative and pro-angiogenic factors. The present study investigated the influence of MIF on the histoarchitecture of the dorsal lobe of the prostate of mice, analyzing the role of the cytokine in the epithelium-stroma interaction of the gland, focusing on the study of muscle cells, fibroblasts and their relationship with epithelial proliferation. Male C57BL/6 wild-type and MIF knockout (MIF-/-) mice were studied at the ages of 30 (prepubertal) and 60 (pubertal) days. The dorsal prostate was removed, weighed and partly fixed in metacarp (for histological processing, staining and immunohistochemistry), the other part frozen for protein extraction and apoptosis analysis. The results showed that the absence of MIF significantly impacts the epithelial compartment, reducing cell proliferation and, consequently, the area of the prostatic epithelium. Furthermore, the MIF-/- group presented an anticipation of prostate development, with more pronounced results in the prepubertal phase, a period in which an increase in fibroblasts, a decrease in epithelial proliferation, an increase in testosterone, among other factors, were observed. However, it was found that the organism demonstrated an attempt to reestablish the homeostasis of the gland, possibly carried out through the activation of secondary proliferation pathways, such as the mTOR and EGF/EGFR pathways, since both have action mediated independently of MIF. Given the importance of the postnatal period in prostate development, we conclude that MIF is relevant in the process of prostate maturation, allowing it to reach a tissue arrangement adequate for the normal performance of physiological and sexual functions in men. These findings highlight the importance of MIF in prostate homeostasis and open avenues for future research on its therapeutic manipulation, since its blockade has been studied in prostate cancer treatments.