Inlfuence Of OEC-secreted Protein IGFBP-5on The Extension Of Axon From Olfactory Receptor Neurons

Olfactory system is a unique part of nervous system in mammals which mainlyincludes olfactory receptor neurons (ORNs)、mitral cells、granule cells and olfactoryensheathing cells. ORNs, the first class neurons in olfactory system, accept the stimulationfrom the odor molecules and achieve the olfactory signal transmission. The formation anddevelopment of ORNs are important for the normal olfactory function. Thus, to understandthe regulation mechanism of ORNs growth will help us elucidate the normal maintainanceand development of olfactory system.Olfactory ensheathing cells (OECs) are unique types of glia cells in olfactory systemthat closely related with ORNs. They share the phenotypes of both schwann cells (SCs)and astrocytes (ACs). During development, they originate from the olfactory placode, wrapolfactory receptor neuron axon bundles and help them to extend through the cribriformplate into the olfactory bulb. It is a crucial part of in-depth understanding of olfactorypathway that how olfactory receptor neurons axons enter into the olfactory bulb and theirdistribution pattern in olfactory bulb. However, little is known about their own biologicalfeatures and their roles during olfactory development, such as: how OECs interact witholfactory nerve; how they help the axons of ORNs enter into the olfactory bulb andinfluence the axons of ORNs sort in the olfactory bulb et al. The interactions betweenOECs and ORNs are important for the maitanance of normal structure and function.Although it has been found that OECs play an important role on the growth, guidance,and unique regenerative capabilities of primary olfactory axons, the components secretedfrom OECs involved in these processes are unclear. In our study we found that OECssecreted protein Insulin-like Growth Factor Binding Protein5(IGFBP-5) can promoteORNs axon growth in an Insulin Growth Factor-I (IGF-I)-dependent manner. The resultsare shown as follows:1. OEC-derived conditioned medium (OEC-CM) promoted ORNs axon growth byORNs neurite outgrowth model in vitro.2. Differentially expressed proteins between OEC-CM and astrocyte-derivedconditioned medium (AC-CM) were identified by2-D gel electrophoresis and masschromatographic analysis. We focused on differentially expressed proteins IGFBP-5. 3. OECs secreted protein IGFBP-5were highly expressed in OECs and olfactorynerve layer of olfactory bulb.4. The results of ORNs neurite outgrowth model confirmed that IGFBP-5promoted ORNs axon growth. Furthermore, neutralizing IGFBP-5in culture medium withanti-IGFBP-5antibody could mitigate this effect.5. In further mechanism study we found that IGF-I receptor inhibitorPicropodophyllin (PPP) can also decrease this effect.In summary, these findings proved that OECs secreted protein IGFBP-5can promoteORNs axon growth in an IGF-I-dependent manner. This study reveals that IGFBP-5secreted from OECs may involve in the growth of ORNs axon.