Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic.
Disruption of canonical TGFβ-signaling in murine coronary progenitor cells by low level arsenic.
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DOI：
10.1016/j.taap.2013.04.035
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发表时间：
2013-10-01
影响因子：
3.8
通讯作者：
Camenisch, Todd D.
中科院分区：
文献类型：
--
作者：
Allison, Patrick;Huang, Tianfang;Broka, Derrick;Parker, Patti;Barnett, Joey V.;Camenisch, Todd D.
接触砷会导致几种类型的癌症和心脏病。冠状动脉疾病是导致缺血性心脏病变的主要因素，然而环境砷在这一疾病过程中的影响尚不清楚。同样，毒物在发育过程中对血管形成和功能的影响还没有研究。在胚胎发育过程中，心外膜经历了增殖、迁移和分化为几种类型的心肌细胞，包括对冠状血管有贡献的平滑肌细胞。转化生长因子β家族的配体和受体是发育中的心脏上皮细胞向间充质细胞转化和分化为冠状动脉平滑肌细胞所必需的。在这项体外研究中，1.34msenite暴露18小时扰乱了小鼠心外膜细胞的发育μ编程，导致心脏间质缺陷。β-2、β受体-3、Snail、Has-2等基因的表达随染砷剂量的增加而降低。转化生长因子β-2细胞信号转导被抑制，当细胞暴露于1.34μ马赛尼特时，磷酸化的Smad2/3被检测到减少。此外，由于接触亚砷酸盐，核聚集物pSmad也有丢失。这些观察与间充质细胞侵入三维胶原胶的阳性细胞减少相一致。但亚砷酸盐不阻断转化生长因子β-2介导的心外膜细胞向平滑肌细胞分化。总体而言，这些结果表明，砷暴露通过干扰转化生长因子β2信号和Smad2的激活来阻止小鼠冠状动脉前体细胞的发育过程中的EMT基因编程，而平滑肌细胞的分化对这种砷毒性是无效的。
Exposure to arsenic results in several types of cancers as well as heart disease. A major contributor to ischemic heart pathologies is coronary artery disease, however the influences by environmental arsenic in this disease process are not known. Similarly, the impact of toxicants on blood vessel formation and function during development has not been studied. During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types including smooth muscle cells which contribute to the coronary vessels. The TGFβ family of ligands and receptors are essential for developmental cardiac epithelial to mesenchymal transition (EMT) and differentiation into coronary smooth muscle cells. In this in vitrostudy, 18 hour exposure to 1.34 μMarsenite disrupted developmental EMT programming in murine epicardial cells causing a deficit in cardiac mesenchyme. The expression of EMT genes including TGFβ2, TGFβ receptor-3, Snail, and Has-2 are decreased in a dose-dependent manner following exposure to arsenite. TGFβ2 cell signaling is abrogated as detected by decreases in phosphorylated Smad2/3 when cells are exposed to 1.34 μMarsenite. There is also loss of nuclear accumulation pSmad due to arsenite exposure. These observations coincide with a decrease invimentinpositive mesenchymal cells invading three-dimensional collagen gels. However, arsenite does not block TGFβ2 mediated smooth muscle cell differentiation by epicardial cells. Overall these results show that arsenic exposure blocks developmental EMT gene programming in murine coronary progenitor cells by disrupting TGFβ2 signals and Smad activation, and that smooth muscle cell differentiation is refractory to this arsenic toxicity.
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影响因子：
5
作者：
Yuan, Yan;Marshall, Guillermo;Smith, Allan H.
通讯作者：
Smith, Allan H.
影响因子：
2.7
作者：
Sánchez NS;Hill CR;Love JD;Soslow JH;Craig E;Austin AF;Brown CB;Czirok A;Camenisch TD;Barnett JV
通讯作者：
Barnett JV
影响因子：
20.1
作者：
Compton, Leigh A.;Potash, Dru A.;Barnett, Joey V.
通讯作者：
Barnett, Joey V.
影响因子：
30.8
作者：
KAARTINEN, V;VONCKEN, JW;GROFFEN, J
通讯作者：
GROFFEN, J
影响因子：
20.1
作者：
SHANAHAN, CM;WEISSBERG, PL;METCALFE, JC
通讯作者：
METCALFE, JC