A Novel Role of the STAT3 Pathway in Brain Inflammation-induced Human Neural Progenitor Cell Differentiation

被引：6

作者：

Chen, E. ^{[1
,2
]}

Xu, D. ^{[1
,2
,5
]}

Lan, X. ^{[1
,2
]}

Jia, B. ^{[1
,2
]}

Sun, L. ^{[1
,2
]}

Zheng, J. C. ^{[1
,2
,3
,4
,5
]}

Peng, H. ^{[1
,2
]}

机构：

[1] Univ Nebraska Med Ctr, Lab Neuroimmunol & Regenerat Therapy, Omaha, NE 68198 USA

[2] Univ Nebraska Med Ctr, Dept Pharmacol & Expt Neurosci, Omaha, NE 68198 USA

[3] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA

[4] Univ Nebraska Med Ctr, Dept Family Med, Omaha, NE 68198 USA

[5] Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Ctr Translat Neurodegenerat & Regenerat Therapy, Shanghai 200092, Peoples R China

来源：

CURRENT MOLECULAR MEDICINE | 2013年 / 13卷 / 09期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

Cytokine; differentiation; inflammation; neural progenitor cell; neurogenesis; STAT3; CENTRAL-NERVOUS-SYSTEM; LEUKEMIA INHIBITORY FACTOR; STEM-CELLS; PROMOTES NEUROGENESIS; ASTROCYTIC DIFFERENTIATION; GLIAL DIFFERENTIATION; ASTROGLIOGENESIS; DISEASE; FETAL; PATHOGENESIS;

D O I：

暂无

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Brain inflammation is a primary pathological driving force of many neurodegenerative disorders. In the destructive process, pro-inflammatory cytokines (IL-1 beta and TNF-alpha), are robustly released, affecting normal neural progenitor cell (NPC) differentiation, and resulting in a vast number of astrocytes and a diminished neural population. A counteractive mechanism is still unknown. In this study, we have identified a link between brain inflammation and the signal transducer and activator of transcription 3 (STAT3) pathway: IL-1 beta and TNF-alpha induce STAT3 activation in NPCs. Then to investigate STAT3's effects on NPC fate, we observed that an inhibition of STAT3 expression by siRNA inhibited astrocytic differentiation and increased neuronal differentiation of human NPCs in fetal bovine serum (FBS)-induced astrocyte differentiation condition. Furthermore, STAT3-targeting siRNA abrogated IL-1 beta and TNF-alpha -induced astrocyte differentiation and partially restored neuronal differentiation. Elimination of STAT3 expression also countered IL-1 beta and TNF-alpha -induced inhibition of proneural bHLH genes, mammalian achaete-schute homologue-1 (Mash1), Neurogenin1 (Ngn1), and Neurogenin2 (Ngn2). These data suggest that a suppression of STAT3 during brain inflammation would inhibit astrogliogenesis and promote neurogenesis. Thus, STAT3 could be a potential target of drug therapy for neurodegenerative disorders.

引用

页码：1474 / 1484

页数：11

共 33 条

[1]

Bal-Price A, 2001, J NEUROSCI, V21, P6480

[2] Regulation of gliogenesis in the central nervous system by the JAK-STAT signaling pathway [J].