The Expression Pattern And Functions Of BRINP1 In Oligodendrocyte Lineage Cells

Objective: Myelin is an important structure for maintaining normal nerve functions,and mainly plays a role in accelerating nerve transmission and protecting axons.Oligodendrocytes(OLs),the myelin forming cells in the Central Nervous System(CNS),construct a concentric sheath-like structure around the axons.They protect axons and provide important nutrition for them.Oligodendrocyte Progenitor Cells(OPCs)are the precursor state of OLs.OPCs continue to regenerate throughout the whole life of mammals,and they are associated to learning new complex skills,which matching the development of brain.At the same time,remyelination is also continuous throughout the life of the mammals.This is a dynamic equilibrium process,which is sensitive to external factors.Myelin is sensitive to the injury factors such as ischemia,hypoxia,inflammation,which can cause axonal demyelination and impair normal nervous system function.Previous studies have shown that myelin regeneration disorder is an important factor in the development of many demyelinating diseases of the CNS.Therefore,finding regulatory factors that promote differentiation and maturation of OPCs is vital for the treatment of these nervous systems demyelinating diseases.BRINP1 is considered to be a Membrane Attack Complex/Perforin(MACPF)protein produced when bone morphogenetic protein(BMP)and retinoic acid(RA)inducing neuron differentiation in embryonic mice.It is regulated by the oligodendrocyte cell-specific promoter Olig2.BRINP1 is mainly and widely expressed throughout the developmental stages of the nervous system.Furthermore,point mutation of Brinp1 gene is associated with multiple sclerosis,a disease characterized by central nervous system white matter demyelinating lesions.It is also associated with mental disorders such as schizophrenia and attention deficit/hyperactivity disorder.But what is the expression pattern of BRINP1 in the nervous system,what the function is,and how it works in demyelinating diseases are still the questions.They are all waiting for us to explore and solve.Methods: First,we combined the means of molecular biology,cell biology,morphology and other research methods to clarify the expression pattern of BRINP1 in various neuronal cells in vitro,as well as during the development of the nervous system of mice.Then we clarified the expression of BRINP1 in the demyelination mouse model.We also studied the effect of BRINP1 overexpression and knockdown lentivirus on the differentiation and development of OPCs.Last but not least,we explored other functions of BRINP1 based on its protein structure.Results: Our study showed that during development,BRINP1 was expressed in PDGFR?+ and CC1+ oligodendrocyte lineage cells.In LPC-induced demyelinating lesions,the expression of BRINP1 was significantly higher than that of the control group.At the same time,we found that RINP1 does not affect the proliferation,apoptosis and migration of OPCs.Overexpression of BRINP1 can promote the differentiation of OPCs in vitro,while knockdown of BRINP1 can reduce the differentiation of OPCs.In addition,we have also found that BRINP1 is an exocrine protein that is secreted in large amounts by undifferentiated OPCs specifically under physiological conditions.It contains a membrane attack complex /Perforin(MACPF)domain that may be involved in the immune response in the nervous system.These results indicated that BRINP1 is specifically expressed in oligodendrocyte lineage cells during myelination and remyelination.It positively regulatedthe differentiation of OPCs and myelination.It possibly become a potential therapeutic target for the treatment of demyelinating disease.Moreover,we have demonstrated the exocrine properties of BRINP1 for the first time,which may be involved in the immune response in the nervous system.