Long term effects of endothelin on rat olfactory mucosa : modulation of neuronal and non neuronal cellular populations dynamics
Résumé
Endothelin-1 (ET-1), also known for its vasoactive effect, acts on cell proliferation/survival in many tissues. We thus investigate the effect of ET-1 on olfactory mucosa (OM) which holds the particularity of renewing from multipotent olfactory progenitors: horizontal (HBC) and globose basal cells (GBC) localised at the basal pole of the olfactory epithelium. We have previously shown that endothelin-1 is locally matured in the OM and that its receptors are present in both olfactory sensory neurons (OSNs) and non-neuronal OM cells (nNCs). We also reported a modulation of odorant detection and OM intercellular communication by ET-1 (see Congar’s poster). In order to evaluate the potential effect of ET-1 on cell survival in both OSNs and nNCs, we developed two primary culture types: i) the whole OM in which OSNs are present; ii) the peeled epithelial layer of OM in which only nNCs are preserved. A serum deprivation in both culture types leads to a massive cellular death, partly through apoptosis. ET-1 treatment rescued part of this cellular loss for all cell types studied. We demonstrated that it goes mostly through an anti-apoptotic effect. Since ET-1 is able to protect cells, we wondered whether ET-1 response could be modulated by stress conditions. Using calcium imaging, we demonstrate firstly that HBCs are activated by ET-1 and secondly that this response appeared only in serum-free medium condition. It suggests a recruitment of endothelin system during a cellular stress. Furthermore, HBCs can be involved in OM renewal, and ET-1 controls proliferation of various cellular types. Therefore, we are currently studying its effect on OM proliferative activity in vivo using BrdU injections: in rats submitted to ET-1 inhibitors nose injections and in ETB receptors-deficient rats. Thus, we can conclude that ET-1 has, at least, a dual role on the OM since on a short term it modulates odorant detection (see above) and on a long term, it enhances the survival of OSNs and nNCs.