Perinatal nicotine exposure induces myogenic differentiation, but not epithelial-mesenchymal transition in rat offspring lung.
Perinatal nicotine exposure induces myogenic differentiation, but not epithelial-mesenchymal transition in rat offspring lung.
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DOI：
10.1002/ppul.23458
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发表时间：
2016-11
影响因子：
3.1
通讯作者：
Rehan, Virender K.
中科院分区：
文献类型：
--
作者：
Sakurai, Reiko;Liu, Jie;Gong, Ming;Bo, Ji;Rehan, Virender K.
围产期尼古丁暴露会改变子代的肺结构和功能；然而，其潜在机制仍未完全清楚。中度围产期尼古丁暴露后是否会发生上皮 - 间质转化（EMT），这一已知的肺部病理学影响因素，尚不明确。
怀孕的、成对喂养的斯普拉格 - 道利大鼠母鼠从胚胎期第6天（e6）到出生后第21天（PND21）每天接受一次安慰剂（稀释剂）或尼古丁[1毫克/千克，皮下注射]。在出生后第21天分离第1代（F1）和第3代（F3）子代的肺，并使用蛋白质印迹分析、定量逆转录聚合酶链反应和免疫组织化学方法检测EMT的证据。为了获得尼古丁诱导的EMT的进一步支持证据，培养胚胎期第19天的原代大鼠肺泡II型（ATII）细胞，并使用尼古丁处理24小时。
α - 平滑肌肌动蛋白、纤连蛋白和钙调蛋白（肌源性分化标志物）的蛋白质水平显著升高。然而，在F1和F3代肺中，表面活性蛋白B和C、胆碱磷酸胞苷酰转移酶 - α（上皮细胞标志物）以及EMT的典型标志物E - 钙黏蛋白、N - 钙黏蛋白和成纤维细胞特异性蛋白（FSP） - 1在尼古丁暴露组和对照组母鼠之间没有显著变化。肺切片的免疫染色以及体外处理的ATII细胞的数据有力地支持了蛋白质印迹分析的数据。
肌源性分子特征增强，但没有EMT的证据，如没有E - 钙黏蛋白缺失或N - 钙黏蛋白和FSP - 1增加所表明的那样，这表明围产期尼古丁暴露不会导致EMT，但会导致肌生成，这是围产期尼古丁暴露的大鼠子代中所见肺表型的主要原因。
Perinatal nicotine exposure alters offspring lung structure and function; however, the underlying mechanisms remain incompletely understood. Whether epithelial– mesenchymal transition (EMT), a known contributor to pulmonary pathology, occurs following moderate perinatal nicotine exposure is not known. Pregnant, pair-fed Sprague Dawley rat dams received either placebo (diluent) or nicotine [1 mg/kg, subcutaneously] once daily from embryonic day (e) 6 to postnatal day (PND) 21. Generation 1 (F1) and 3 (F3) offspring lungs were isolated at PND 21, and using Western analysis, q-RT-PCR and immunohistochemistry examined for evidence of EMT. To gain further supportive evidence for nicotine-induced EMT, embryonic day 19 primary rat lung alveolar type II (ATII) cells were cultured and treated with nicotine for 24 hr. Protein levels of α-smooth muscle actin, fibronectin, and calponin (myogenic differentiation markers) increased significantly. However, surfactant proteins B and C, and cholinephosphate cytidylyltransferase- α (epithelial cell markers), as well as the typical markers of EMT, E-cadherin, N-cadherin, and fibroblast specific protein (FSP)-1, in both F1 and F3 generation lungs, showed no significant change between the nicotine exposed and control dams. Immunostaining of lung sections and data from in vitro treated ATII cells strongly supported the Western data. Enhanced myogenic molecular profile, without evidence of EMT, as evidenced by the absence of the loss of E-cadherin or gains in N-cadherin and FSP-1, suggest that perinatal nicotine exposure does not result in EMT, but it leads to myogenesis, which predominantly accounts for the lung phenotype seen in perinatally nicotine exposed rat offspring.
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影响因子：
9.3
作者：
Rehan VK;Liu J;Naeem E;Tian J;Sakurai R;Kwong K;Akbari O;Torday JS
通讯作者：
Torday JS
影响因子：
11.2
作者：
Pillai S;Trevino J;Rawal B;Singh S;Kovacs M;Li X;Schell M;Haura E;Bepler G;Chellappan S
通讯作者：
Chellappan S
影响因子：
5
作者：
Rehan VK;Asotra K;Torday JS
通讯作者：
Torday JS
影响因子：
2.5
作者：
Chen, Chung-Ming;Chou, Hsiu-Chu;Huang, Liang-Ti
通讯作者：
Huang, Liang-Ti
DOI：
10.1152/ajplung.00078.2013
发表时间：
2013-10-01
影响因子：
4.9
作者：
Rehan, Virender K.;Liu, Jie;Torday, John S.
通讯作者：
Torday, John S.