BMP2 promotes differentiation of nitrergic and catecholaminergic enteric neurons through a Smad1-dependent pathway
BMP2 promotes differentiation of nitrergic and catecholaminergic enteric neurons through a Smad1-dependent pathway
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DOI：
10.1152/ajpgi.00343.2009
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发表时间：
2010-03-01
影响因子：
4.5
通讯作者：
Srinivasan, Shanthi
中科院分区：
文献类型：
--
作者：
Anitha, Mallappa;Shahnavaz, Nikrad;Srinivasan, Shanthi
Anitha M, Shahnavaz N, Qayed E, Joseph I, Gossrau G, Mwangi S, Sitaraman SV, Greene JG, Srinivasan S. BMP2通过smad1依赖通路促进肠内氮和儿茶酚胺能神经元分化。[J] .中国生物医学工程学报，2016,31(2):557 - 557。首次发表于2009年12月10日；doi: 10.1152 / ajpgi.00343.2009。骨形态发生蛋白（BMP）家族是一类转化生长因子（tgf - β）超家族分子，与神经元分化有关。我们研究了BMP2和胶质细胞系来源的神经营养因子（GDNF）在诱导肠神经元分化中的作用及其信号转导通路。研究使用一种新的小鼠胎儿肠神经元细胞系（IM-FEN）和原代肠神经元进行。将肠内神经元分别在培养液、GDNF （100 ng/ml）、BMP2 （10 ng/ml）或两者（GDNF + BMP2）存在下培养，通过神经突长度、神经元分化标志物（神经丝介质多肽和β - iii -微管蛋白）和神经递质表达[神经肽Y （NPY）、神经元一氧化氮合酶（nNOS）、酪氨酸羟化酶（TH）、胆碱乙酰转移酶（ChAT）和P物质]来评估分化情况。与对照和gdnf处理的神经元相比，BMP2增加了肠神经元的分化（P < 0.001）。BMP2增加了成熟神经元标志物的表达（P < 0.05）。BMP2促进表达NPY-、nNOS-和th的神经元的分化（P < 0.001），但对胆碱能神经元（ChAT, Substance P）的表达没有影响。1-甲基4-苯基吡啶（MPP+）与单独MPP+培养的神经元相比，在BMP2存在下培养的神经元表达th的神经元数量更多（P < 0.01）。Smad信号转导通路与tgf - β信号传导有关。BMP2诱导Smad1磷酸化，Smad1 siRNA存在时，BMP2对肠神经元分化的影响显著降低，提示Smad1在BMP2诱导的分化中起作用。BMP2对儿茶酚胺能神经元的影响可能对胃肠道运动障碍具有治疗意义。
Anitha M, Shahnavaz N, Qayed E, Joseph I, Gossrau G, Mwangi S, Sitaraman SV, Greene JG, Srinivasan S. BMP2 promotes differentiation of nitrergic and catecholaminergic enteric neurons through a Smad1-dependent pathway. Am J Physiol Gastrointest Liver Physiol 298: G375-G383, 2010. First published December 10, 2009; doi: 10.1152/ajpgi.00343.2009.-The bone morphogenetic protein (BMP) family is a class of transforming growth factor (TGF-beta) superfamily molecules that have been implicated in neuronal differentiation. We studied the effects of BMP2 and glial cell line-derived neurotrophic factor ( GDNF) on inducing differentiation of enteric neurons and the signal transduction pathways involved. Studies were performed using a novel murine fetal enteric neuronal cell line (IM-FEN) and primary enteric neurons. Enteric neurons were cultured in the presence of vehicle, GDNF (100 ng/ml), BMP2 (10 ng/ml), or both (GDNF + BMP2), and differentiation was assessed by neurite length, markers of neuronal differentiation (neurofilament medium polypeptide and beta-III-tubulin), and neurotransmitter expression [neuropeptide Y (NPY), neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase (TH), choline acetyltransferase (ChAT) and Substance P]. BMP2 increased the differentiation of enteric neurons compared with vehicle and GDNF-treated neurons (P < 0.001). BMP2 increased the expression of the mature neuronal markers (P < 0.05). BMP2 promoted differentiation of NPY-, nNOS-, and TH-expressing neurons (P < 0.001) but had no effect on the expression of cholinergic neurons (ChAT, Substance P). Neurons cultured in the presence of BMP2 have higher numbers of TH-expressing neurons after exposure to 1-methyl 4-phenylpyridinium (MPP+) compared with those cultured with MPP+ alone (P < 0.01). The Smad signal transduction pathway has been implicated in TGF-beta signaling. BMP2 induced phosphorylation of Smad1, and the effects of BMP2 on differentiation of enteric neurons were significantly reduced in the presence of Smad1 siRNA, implicating the role of Smad1 in BMP2-induced differentiation. The effects of BMP2 on catecholaminergic neurons may have therapeutic implications in gastrointestinal motility disturbances.