A Shh/miR-206/BDNF Cascade Coordinates Innervation and Formation of Airway Smooth Muscle

被引:68
|
作者
Radzikinas, Kelsi [1 ]
Aven, Linh [1 ]
Jiang, Zhihua [1 ]
Thanh Tran [1 ]
Paez-Cortez, Jesus [1 ]
Boppidi, Karthik [1 ]
Lu, Jining [1 ]
Fine, Alan [1 ]
Ai, Xingbin [1 ]
机构
[1] Boston Univ, Sch Med, Ctr Pulm, Dept Med, Boston, MA 02118 USA
来源
JOURNAL OF NEUROSCIENCE | 2011年 / 31卷 / 43期
基金
美国国家卫生研究院;
关键词
NERVE GROWTH-FACTOR; SONIC HEDGEHOG; NEUROTROPHIC FACTOR; MOUSE; EXPRESSION; TISSUE; MORPHOGENESIS; MESENCHYME; MICRORNAS; RECEPTOR;
D O I
10.1523/JNEUROSCI.2745-11.2011
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Dysfunctional neural control of airway smooth muscle (ASM) is involved in inflammatory diseases, such as asthma. However, neurogenesis in the lung is poorly understood. This study uses mouse models to investigate developmental mechanisms of ASM innervation, a process that is highly coordinated with ASM formation during lung branching morphogenesis. We show that brain-derived neurotrophic factor (BDNF) is an essential ASM-derived signal for innervation. Although BDNF mRNA expression is temporally dissociated with ASM formation and innervation, BDNF protein is coordinately produced through post-transcriptional suppression by miR-206. Using a combination of chemical and genetic approaches to modulate sonic hedgehog (Shh) signaling, a pathway essential for lung branching and ASM formation, we show that Shh signaling blocks miR-206 expression, which in turn increases BDNF protein expression. Together, our work uncovers a functional cascade that involves Shh, miR-206 and BDNF to coordinate ASM formation and innervation.
引用
收藏
页码:15407 / 15415
页数:9
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