Objective: The mature nerves have two phenotypes of Schwann cells, myelinating (MSC) and nonmyelinating (nMSC).Schwann cells abnormal hyperplasia, but fail to form normal myelination during chronic peripheral nerve diseases.This situations hint that paraplastic Schwann cells are not simplex repair reaction.We are very interested to follow subjects: What factor mediates normal Schwann cell become nMSC ? How to cognitive that regulative mechanism of the myelin gene expression? In this series of research, We will try to find out the relationship of Schwann cells differentiation and myelin sheath re-formation.Methods and Results: the three processes at different levels of biological system, including the patients nerve biopsy with neuropathies (200 cases), Peripheral neuropathy rodent models, and primary culture neurons/Schwann cells.Two important genes (MBP and PMP22) to be detected in "promyelinating" stage of hyperplasia of Schwann cells during chronic peripheral nerves injure by immunohistochemistry staining, measured and analyzed pathologically and statistically in a context of the morphological impression gained from light microscopy and electron microscopy.Those results point out that the locations of the two proteins were not completely identical.PMP22 more represented the status of Schwann cell than MBP.Using laser capture microdissection (LCM) mathods, obtain the MSC and nMSC from nerve biopsy of CPN.Then detect the mRNA of Myelin-associated gene (MAG,PMP22) through Realtime-PCR.Correlate with quantification several components of peripheral nerve tissue with Electronic Microscopy(EM), to discover their relationship.Statistical analysis shows that Myelin-associated gene MAG and PMP22 have some correlation with some mophological changes.We established the Schwann cell and nerve cell co-culture model using RSC96 cell and ventral spinal cord4.1 cell (VSC4.1).Added TNFα, IFNγ and IGF-1 etc stimulating factorin in vitro.The results show that low density TNFα and IFNγ not only promotes Schwann cells proliferation, but also up regulates Myelin-associated Glycoprotein expression in SC with NC co-culture in vitro.IGF-1 had no effect on the cell proliferation, but can change the Cells form characteristics on ultrastructure, and increase the gene expression of MBP and PMP22.Conclusion: In this series of research, We try to find out The relationship of Schwann cells differentiation and myelin sheath re-formation.Discern the molecular mechanisms of MAG, PMP22 and MBP action be important contribution both for understanding re-myelination and for designing future treatments for chronic peripheral nerve diseases.