FIBRONECTIN AND MATRIX METALLOPROTEINASE 9 IN THE HYPOTHALAMIC SUPRAOPTIC-PARAVENTRICULAR NUCLEI: EFFECTS OF SALT LOADING

Introduction:The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, which control hydro-osmotic homeostasis, via vasopressin, undergo morphological changes involving magnoneuron cells (MN), astrocytes and extracellular matrix (ECM). Osmotic stimulation by salt loadind induces MN juxtaposition, without astrocytic-end feet coverage but with more synapses. In addition, astrocytes and endothelial cells proliferation occurs with local angiogenesis.Aim of the work: In this work, to clarify molecular mechanisms of angiogenesis accompanying morphological plasticity associated to saline load, we studied the distribution of proteins involved in interactions between intra- and extra-cellular spaces, namely fibronectin (FN), dystrophins (Dps) and β-dystroglycan (βDG), as an ECM receptor. Also, we analyzed the distribution of the Matrix metalloproteinase (MMP9), implicated in ECM remodeling and the fibroblast growth factor (FGF2), an angiogenic factor.Material and methods: Adult Balb/c mice (12 animals) were divided into two groups, control group (Ctl) received water and salt loaded group (SL) received saline-water (NaCl 2%) ad libitum during eight days. Water intake was measured daily during the eight days, and plasma osmolality was measured. Sections of the SON and PVN obtained were stained for histological study and immunohistochemistry for FN, βDG, Dps, MMp9 and FGF2was conducted.Results: The SON and PVN, FN, Dps, βDG, MMP9 and FGF2 were localized around vessels and MN. After saline load, the level and/or distribution of these molecules modified. The observed morphological changes require ECM remodeling where βDG and ECM components are used as target by MMP9. Conclusion: MMP9 would facilitate the retraction of astrocyte expansions and the release of FGF2, sequestered in the ECM. Once released, FGF2 will interact with its vascular receptors, inducing the synthesis of FN. This is involved in the angiogenesis mechanisms through its role in the assembly of the newly formed vascular basement membrane.