Leptin Play the Key Role in Astroglial Differentiation of Mouse Neural Stem Cells and Regulated the STAT3 Signaling Through Jak-STAT3 Pathway

WANG Ya-nan, YANG Mi, YU Li-hua. et al

Abstract

To investigate the effect of Leptin on differentiation of nueral stem cell and explore the underline molecular mechanism. Methods Co-culture neural stem cell with different concentration of Leptin (0, 0.05, 0.2, 0.5, 1, 2 mg/L), the effect of Leptin on differentiation of nueral stem cell was analyzed. After treated the nueral stem cell with inhibitors of Jak-STAT3 〔Janus family tyrosine kinases (Jak kinases) and signal transducers and activators of transcription (STAT proteins) 〕and PI3k-Akt 〔phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)〕, the STAT3, phosphorylated-STAT3, Akt, phosphorylated-Akt levels and GFAP were detected with western blot and fluoroimmunoassay respectively. Results Morphology observation found nueral stem cell to change to astrocyte. An increased astrocyte marker (GFAP) in Leptin group but not Tuj-1 or MBP with fluoroimmunoassay and western blot detection was observed. The expression of GFAP began at 24 h after co-culture, and increased consistent with the concentration of Leptin. Jak-STAT3 inhibitors but not PI3k-Akt inhibitors decreased the expression of phosphorylated-STAT3, and accompanily decreased the expression of GFAP. Conclusion Leptin may have an effect on the astroglial differentiation on neural stem cells through the JAK-STAT3 pathway but not PI3k-Akt pathway.

 

Keywords: Leptin, Neural stem cells, Astrocyte, Induced differentiation 

 

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References


Reynolds BA, Weiss S. Generation of neurons and astrocytes from isolated cells of the adult mammalian central nervous system. Science. 1992;255(5052): 1707-1710.

Zhao С, Deng W, Gage FH, et al. Mechanisms and functional implications of adult neurogenesis. Cell ,2008; 132(4): 645-660.

Leung CT, Coulombe PA, Reed RR. Contribution of olfactory neural stem cells to tissue maintenance and regeneration. Nat Neurosci,2007; 10(6) :720-726.

Ilkhanizadeh S, Teixeira AI, Hermanson O. Inkjet printing of macromolecules on hydrogels to steer neural stem cell differentiation. Biomaterials,2007;28(27):3936-3943.

Matsuzaki F. Asymmetric division of Drosophila neural stem cells: a basis for neural diversity. Curr Opin Neurobiol,2000; 10 (1): 38-44.

Chia W, Yang X. Asymmetric division of Drosophila neural progenitors. Curr Opin Genet Dev,2002; 12(4) :459-464.

Molina-Hernandez A, Velasco I. Histamine induces neural stem cell proliferation and neuronal differentiation by activation of distinct histamine receptors. J Neurochem, 2008; 106 ( 2 ); 706- 717.

Tong X, Zitserman D, Serebriiskii I. et al. Numb independently antagonizes Sanpodo membrane targeting and Notch signaling in Drosophila sensory organ precursor cells. Mol Biol Cell»2010;21 (5):802-810.

Rosi MC, Luccarini I, Grossi C, et al. Increased Dickkopf-1 expression in transgenic mouse models of neurodegenerative disease. J Neurochem, 2010; 112(6): 1539-1551.

Angulo E.Casado V, Mallol J. et al. Al adenosine receptors accumulate in neurodegenerative structures in Alzheimer disease and mediate both amyloid precursor protein processing and tau phosphorylation and translocation. Brain Pathol,2003; 13(4);440-451.

Kumar AA, Kumar SR. Narayanan R .et al. Autologous bone marrow derived mononuclear cell therapy for spinal cord injury: a phase I /II clinical safety and primary efficacy data. Exp Clin Transplant,2009;7(4):241-248.

Sun J, Gao Y, Yang L, et al. Neural-tube-derived neuroepithelial stem cells; a new transplant resource for Parkinson's disease. Neuroreport,2007; 18( 6): 543-547.

Avraham Y, Dayan M, Lassri V. et al. Delayed leptin administration after stroke induces neurogenesis and angiogenesis. J Neurosci Res,2013;91(2): 187-195.

Guo Z. Jiang H. Xu X. et al. Leptin-mediated cell survival signaling in hippocampal neurons mediated by JAK STAT3 and mitochondrial stabilization. J Biol Chem, 2008; 283 ( 3 ): 1754- 1763.

Petersen PH, Zou K, Krauss S, et al. Continuing role for mouse Numb and Numbl in maintaining progenitor cells during cortical neurogenesis. Nat Neurosci,2004 ; 7(8) ;803-811.

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Bayes-Genis A, Conover СА, Overgaard МТ, et al. Pregnancy-associated plasma protein A as a marker of acute coronary syndromes. N Engle J Med, 2001; 345 ( 14 ); 1022- 1029.

Bayes-Genis A, Conover С A, Schwartz RS. The insulin-like growth factor axis: a review of atherosclerosis and restenosis. Circ Res,2000;86(2); 125-130.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 1976; 7( 72);248-254.

Gaidamauskas Е, Gyrup С, Boldt HB, et al. IGF dependent modulation of IGF binding protein ( IGFBP) proteolysis by pregnancy-associated plasma protein-A ( PAPP-A ): multiple PAPP-A-IGFBP interaction sites. Biochim Biophys Acta,2013; 1830(3) ;2701-2709.

WoelfleJ, Roth CL, Wunsch R, et al. Pregnancy-associated plasma protein A in obese children: relationship to markers and risk factors of atherosclerosis and members of the IGF system. Fur J Endocrinol,2011; 165(4);613-622.

Harrington SC, Simari RD, Conover CA. Genetic deletion of pregnancy-associated plasma protein A is associated with

Conover CA, Harrington SC, Bale LK. Differential regulation of pregnancy associated plasma protein-A in human coronary artery endothelial cells and smooth muscle cells. Growth Horm IGF Res,2008; 18(3):213-220.

Conover CA, Bale LK, Harrington SC, et al. Cytokine stimulation of pregnancy-associated plasma protein A expression in human coronary artery smooth muscle cells; inhibition by resveratrol. Am J Physiol Cell Physiol, 2006 ; 290 (10) :C183-C188.

Higashi Y, Sukhanov S, Anwar A, et al. Aging, atherosclerosis, and IGF-1. J Gerontol A Biol Sci Med Sci, 2012;67(6):626-639.

Harrington SC. Genetic deletion of pregnancy -associated plasma protein A is associated with resistance to atherosclerotic lesion development in apolipoprotein E-deficient mice challenged with a high-fat diet. Circ Res, 2007 ; 100( 12): 1696- 1702.

Mason EJ, Grell JA.Wan J, et al. Insulin-like growth factor (IGF)- 1 and IGF- 11 contribute differentially to the phenotype of pregnancy associated plasma protein-A knock-out mice. Growth Horm IGF Res,2011 ;21(5) :243-247.

Shai SY, Sukhanov S, Higashi Y. et al. Smooth muscle cell-specific insulin-like growth factor-1 overexpression in Apoe—/— mice does not alteratherosclerotic plaque burden but increases features of plaque stability. Arterioscler Thromb Vase Biol,2010;30( 10); 1916-1924.


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