Leukemia inhibitory factor inhibits neuronal terminal differentiation through STAT3 activation.

Moon C; Yoo JY; Matarazzo VSung YKKim EJRonnett GV

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Leukemia inhibitory factor inhibits neuronal terminal differentiation through STAT3 activation.

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The discovery of stem cells in the adult central nervous system raises questions concerning the neurotrophic factors that regulate postnatal neuronal development. Olfactory receptor neurons (ORNs) are a useful model, because they are capable of robust neurogenesis throughout adulthood. We have investigated the role of leukemia inhibitory factor (LIF) in postnatal neuronal development by using ORNs as a model. LIF is a multifunctional cytokine implicated in various aspects of neuronal development, including phenotype determination, survival, and in response to nerve injury. LIF-deficient mice display significant increases, both in the absolute amount and in the number of cells expressing olfactory marker protein, a marker of mature ORNs. The maturation of ORNs was significantly inhibited by LIF in vitro. LIF activated the STAT3 pathway in ORNs, and transfection of ORNs with a dominant negative form of STAT3 abolished the effect of LIF. These findings demonstrate that LIF negatively regulates ORN maturation via the STAT3 pathway. Thus, LIF plays a critical role in controlling the transition of ORNs to maturity. Consequently, a population of ORNs is maintained in an immature state to facilitate the rapid repopulation of the olfactory epithelium with mature neurons during normal cell turnover or after injury.

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《Proceedings of the National Academy of Sciences of the United States of America》 |2002年第13期|9015-9020|共6页
作者
Moon C; Yoo JY; Matarazzo VSung YKKim EJRonnett GV;
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作者单位

Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.;

ubhealth.ku.dk;

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收录信息美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种英语
中图分类自然科学总论;
关键词
Cell Differentiation; DNA-Binding Proteins; Growth Inhibitors; Lymphokines; 细胞分化; DNA结合蛋白质类; 生长抑制物; 淋巴因子; 嗅觉受体神经元; 反式作用因子;

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1. Leukemia inhibitory factor/differentiation‐stimulating factor (LIF/D‐factor): Regulation of its production and possible roles in bone metabolism [J] . Yoshiko Ishimi, Etsuko Abe, Cheng He JinChisato MiyauraMei Hua HongMidori OshidaHisashi KurosawaYuri YamaguchiMikio TomidaMotoo HozumiTatsuo Suda journal of cellular physiology . 1992,第1期

机译：Leukemia inhibitory factor/differentiation‐stimulating factor (LIF/D‐factor): Regulation of its production and possible roles in bone metabolism
2. Separate functions for the two modules of the membrane-proximal cytokine binding domain of glycoprotein 190, the leukemia inhibitory factor low affinity receptor, in ligand binding and receptor activation. [J] . Voisin MathieuBenoit, Bitard Juliette, Daburon SophieMoreau JeanFrancoisTaupin JeanLuc The Journal of biological chemistry . 2002,第16期

机译：Separate functions for the two modules of the membrane-proximal cytokine binding domain of glycoprotein 190, the leukemia inhibitory factor low affinity receptor, in ligand binding and receptor activation.
3. Leukaemia Inhibitory Factor or Related Factors Promote the Differentiation of Neuronal and Astrocytic Precursors within the Developing Murine Spinal Cord [J] . Linda J. Richards, Trevor J. Kilpatrick, Renee DuttonSeong‐Seng TanDavid P. GearingPerry F. BartlettMark Murphy european journal of neuroscience . 1996,第2期

机译：Leukaemia Inhibitory Factor or Related Factors Promote the Differentiation of Neuronal and Astrocytic Precursors within the Developing Murine Spinal Cord
4. Fingolimod inhibits proliferation and epithelial–mesenchymal transition in sacral chordoma by inactivating IL-6/STAT3 signalling [O] . Jiaqi Wang, Wenhao Hu, Xiaowen Du, 2020

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5. Molecular study of differentially expressed genes in tumor necrosis factor alpha (TNF-α) induced WEHI 3B JCS myeloid leukemia cell differentiation. [O] . 1999

机译：molecular study of differentially expressed genes in tumor necrosis factor alpha (TNF-α) induced WEHI 3B JCs myeloid leukemia cell differentiation.

Leukemia inhibitory factor inhibits neuronal terminal differentiation through STAT3 activation.

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