Fator de inibição da migração de macrófagos (MIF) e sua função no desenvolvimento da próstata lateral de camundongos

Abstract

In rodents, prostate organogenesis has important proliferative and apoptotic postnatal stages, culminating in the formation of a gland with well-defined lobes and differentiated morphological characteristics. The macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine, related to several proliferative signaling pathways, expressed in the prostate glandular epithelium and overexpressed in pathological conditions. However, its function in the development and function of the gland has not yet been elucidated. This study aimed to deepen the understanding of the role of MIF in the postnatal development of the lateral prostate of prepubertal and pubertal mice and to understand whether its absence has an impact on the gland. For this, C57BL/l6 and MIF knockout mice were used at the ages of 30 and 60 days. The animals' blood was collected for testosterone quantification by ELISA. Histological sections were used for general study of the lateral lobe (HE staining), collagen fibers (Picrosirius-Hematoxylin staining) and immunohistochemistry for cell proliferation, fibroblasts, and smooth muscle cells. Part of the samples was frozen for protein extraction and measurement of caspase-3 levels. A reduction in epithelial cell proliferation was observed in prepubertal MIF knockout mice compared to the control, as well as an increase in stromal proliferation at 60 days. Apoptosis in these individuals is higher throughout development and in the pubertal phase. The frequency of fibroblasts did not undergo significant changes, but the amount of collagen in MIF-/- 30 days is lower compared to wild-type. In addition, these animals showed a greater reduction in the frequency of smooth muscle cells throughout development. Testosterone levels were increased in MIF-/- of prepubertal age. These data are reflected in stereology, in which MIF-/- animals had a reduction in the epithelium greater than expected and a smaller increase in the lumen and did not present the expected decreases in muscular and nonmuscular throughout prepubertal to pubertal development. In addition, when compared to wild mice of the same age, MIF-/- 30 days had reduced stromal area. Thus, we can conclude that MIF signaling is relevant for the correct development of the prostate and that its absence impacts the lateral prostate lobe through the reduction of important components of structure and contractility.