Effect Of Hemopexin On Neurogenesis In The Olfactory Epithelium

Olfaction is an important sense for animals.The mammalian olfactory system consists of the central olfactory bulb and olfactory cortex,and the peripheral olfactory mucosa which is divided into the olfactory epithelium and the lamina propria.The olfactory epithelium contains basal cells,olfactory receptor neurons and sustentacular cells.Basal cells,which reside in the basal layer of olfactory epithelium,close to the lamina propria,have been identified as candidate stem cells of olfactory epithelium.Upon the basal layer,the olfactory receptor neurons(ORNs)that are differentiated from basal cells are primary sensory neurons of olfactory system.In the process of differentiating into mature ORNs,the cell bodies of them migrate from the basal layer to the apical layer,which makes ORNs in different degrees of differentiation located in different layer.The cell bodies of immature ORNs are near the basal layer and the cell bodies of mature ORNs are on them close to the apical layer.The neurogenesis of the olfactory epithelium plays an important role in maintaining olfactory function.The neurogenesis of OE is an extremely complicated process,which contains the proliferation,differentiation and maturation of olfactory stem cells.Each stage is subject to strict regulation.However,the mechanism of the regulation is not well understood.Hemopexin is a plasma glycoprotein belonging to the acute phase proteins family.More interestingly,Hemopexin is expressed in peripheral nervous system(PNS)and up-regulated in the process of axonal degeneration.These suggest that hemopexin may take part in the regeneration of nerve injury.Hemopexin,matrix metalloproteinases(MMPs)and vitronectin all share the same domain made up by 4?-helix,which is called Hemopexin-like domain.Studies have shown that MMPs and vitronectin can regulate the hyperplasia and differentiation of many cells even neurogenesis by this domain.There is little research about the function of hemopexin in nervous system.And there is no report of hemopexin involving in olfactory neurogenesis.This objective of this research is trying to explore the effect and mechanism of hemopexin in the ORNs neurogenesis.The results are as follows:1.The morphological analysis of the olfactory epithelium of the hemopexin knock-out mice showed that the defect of hemopexin makes the thickness and density of olfactory epithelium both decrease;the density of mature ORNs decrease;the density of immature ORNs increase and some immature ORNs appear in the upper layer where mature ORNs reside.2.Using immunohistochemical methods,our research further found that no significant difference in the density of proliferation cells is observed between the two genotypes,but the density of apoptosis cells increase in the hemopexin-deficient mice.Moreover,no significant difference in the density of CK5+ cells is observed between the two genotypes,indicating hemopexin-knockout does not affect the maintenance and self-renew of HBCs.3.By means of olfactory function behavior experiment,we detected that hemopexinknock-out mice still have the ability to detect odorants but lose the fine olfactory function to distinguish between structurally similar odorants.In brief,our research found that hemopexin play an important role in the process of the neurogenesis of the olfactory epithelium.Hemopexin can promote ORNs maturation,inhibit ORNs apoptosis and maintain fine olfactory function.This study will not only help us to get a further understand of the regulation of olfactory epithelium neurogenesis and the mechanism of neurogenesis,but also serve as a theoretical underpinning for the potential therapeutic value of hemopexin for olfactory dysfunction.