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SHP2 regulation of oligodendrocyte differentiation

Author: LiZuoZuo
Tutor: HeCheng；LiuXiuJie
School: Second Military Medical University
Course: Basic Medical
Keywords: OLs Differentiation Tyrosine phosphatase SHP2 T3
CLC: R329
Type: Master's thesis
Year: 2010
Downloads: 68
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Abstract

Multiple sclerosis (MS) patients with central nervous system (CNS) manifestations of progressive loss of myelin, myelin damage can not be regenerated. Myelin formation consists of a series of processes: stem cells differentiate into oligodendrocyte precursor cells (OPCs), OPCs proliferation, migration, differentiation and maturation, thereby surrounding the axon myelination crunch. OPCs remyelination process of differentiation is the key to one of the latest point of view, OPCs differentiation is difficult to regenerate myelin disruption is one of the main. However, OPCs differentiation-related adjustment mechanism is not very clear. OLs differentiation regulation by many growth factors, such as CNTF, NT3 and ErBb2 so on. Growth factors acting on OLs done through downstream signaling, phosphorylation of signaling molecules of these signal transduction in the main event. Studies have shown that, PI3K/Akt, Fyn / Rho, MAPK phosphorylation of other molecules in the OLs cell differentiation and myelination process played an important role. Intracellular signaling molecule phosphorylation levels by phosphorylation of kinases and phosphatases in the regulation, at present, about phosphokinase and the relationship between myelination has become a hot spot, but between phosphatase and myelination little research. Sodium orthovanadate (SOV), is a broad spectrum inhibitor of phosphatase, can be widely inhibit the phosphatase activity, can inhibit the tyrosine dephosphorylation point raised growth factor receptor tyrosine kinase-associated signal. SHP2 is a cytosolic non-receptor tyrosine phosphatase, widely expressed in the nervous system. Study found that, SHP2 knockout neural stem cells differentiate into oligodendrocytes significantly reduced the number, SHP2 after ischemic injury in the brain was significantly increased. However, SHP2 is involved in regulating cell differentiation OLs been reported. This study consists of five parts: 1. E18 through SOV feeding pregnant rats given SOV perinatal rats treated immunohistochemical detection of neonatal day 7 (P7) SD rat brain corpus callosum MBP expression levels MBP signal was observed significantly reduced; 2. vitro purified OPCs, treatment with different concentrations of SOV found 25gM and higher concentrations could significantly inhibit the OLs differentiation; 3 using a specific inhibitor of tyrosine phosphatase (PTP inhibitor Ⅳ) processing found 2μM concentrations above significantly inhibited OLs cell differentiation; 4. vitro purified OPCs, SHP2 detected in oligodendrocyte precursors and mature stage were expressed. Immunohistochemical staining further confirmed SHP2 in rat brain oligodendrocytes lines exist expression; 5. Application RNA i interference, overexpression of transfected into OPCs, OLs cell processes found SHP2 promote branching and growth, but also can promote MBP expression. SHP2 promote the role of OLs cell differentiation by extracellular stimuli affect T3. In conclusion, our study shows, SHP2 as a new differentiation regulatory factor involved in the regulation OLs process of differentiation.

SHP2 regulation of oligodendrocyte differentiation

Abstract

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