Zeb2 regulates the increase of astrocytes and recovery of motor function after spinal cord injury in mice by EMT process

Objective:Explore the effect of Zeb2 gene on spinal cord injury(SCI)in mice and its possible mechanism.Methods:Thirty-six healthy male mice were randomly divided into 3 groups:control group(12 in sham group),spinal cord injury group(12 in SCI group),and spinal cord injury Zeb2 conditional knockout group(12 in Zeb2cKO group).SCI mouse model,followed by spinal cord motor function score(Basso.Beattie.Bresnahan scale,BBB scale)within 2W to assess the recovery of motor function of mice.After the experiment 2W,the mice were euthanized to take spinal cord,and 6 mice were randomly selected from each group for immunization Blotting was used to detect the expression levels of Zeb2,astrocyte markers(glial fibrillary acidic protein,GFAP)and epithelial-to-mesenchymal transitions(EMT)related proteins(E-cadherin,N-cadherin),Quantitative PCR was used to detect Zeb2 mRNA,and the other 6 mice were used for pathology and immunofluorescence to evaluate the area of SCI area,Zeb2 and GFAP expression.Results:Compared with the sham group,the expression level of Zeb2,GFAP,N-cadherin,Zeb2 mRNA level,spinal cavity area,Zeb2,GFAP positive rate and BBB score were significantly increased in the SCI group,and the difference was statistically significant(P<0.05).The expression level of E-cadherin was significantly reduced,and the difference was statistically significant(P<0.05).Compared with the SCI group,the Zeb2cKO group had Zeb2,GFAP,N-cadherin expression,Zeb2 mRNA level,Zeb2,GFAP positive rate and BBB score.Significantly lower,the difference is statistically significant(P<0.05),while the spinal cord cavity area and E-cadherin expression level are significantly increased,and the difference is statistically significant(P<0.05).Conclusion:These findings indicate that Zeb2 promotes the increase of astrocytes and restores nerve function after injury.Newlyborn astrocytes have Zeb2 mRNA expression,but only induce protein expression after injury.The conditional knockout of Zeb2 can reduce the proliferation of astrocytes,produce larger lesions,and delay the recovery of motor function.ZEB2 is an important regulator of astrocyte proliferation after SCI,and promotes the formation of astrocyte scarring and the recovery of motor function after SCI,which may be carried out through a process similar to EMT.