Mir-206 regulates pulmonary artery smooth muscle cell proliferation and differentiation.
Mir-206 regulates pulmonary artery smooth muscle cell proliferation and differentiation.
复制标题
DOI：
10.1371/journal.pone.0046808
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kolliputi N
中科院分区：
文献类型：
--
作者：
Jalali S;Ramanathan GK;Parthasarathy PT;Aljubran S;Galam L;Yunus A;Garcia S;Cox RR Jr;Lockey RF;Kolliputi N
肺动脉高压(PAH)是一种以肺动脉平滑肌细胞过度增殖为特征的进行性破坏性疾病。研究表明，PAH和癌症共享一种以细胞过度增殖为特征的抗凋亡状态。MicroRNA-206(miR-206)是已知的调节增殖的基因，与多种类型的癌症有关。然而，miR-206在PAH中的作用尚未被研究。本研究假设miR-206可能在PASMCs的增殖中起作用。在本研究中，我们研究了miR-206在正常和高血压小鼠PASMC中的表达模式。研究miR-206对体外培养的人肺血管平滑肌细胞(HPASMCs)增殖、凋亡及平滑肌细胞标志物的影响。MIR-206在小鼠PASMCs中的表达与右室收缩压升高相关。HPASMCs中miR-206水平的降低导致细胞增殖增加和凋亡减少，这些作用被miR-206的过表达所逆转。MIR-206的过表达也增加了平滑肌细胞分化标记物α-平滑肌肌动蛋白和钙蛋白的水平，暗示其在SMC分化中的重要作用。MIR-206过表达下调了Notch-3的表达，这是PAH发生发展的关键因素。这些结果提示miR-206可能是PASMCs增殖、凋亡和分化的潜在调节因子，可作为治疗PAH的新策略。
Pulmonary Arterial Hypertension (PAH) is a progressive devastating disease characterized by excessive proliferation of the Pulmonary Arterial Smooth Muscle Cells (PASMCs). Studies suggest that PAH and cancers share an apoptosis-resistant state featuring excessive cell proliferation. MicroRNA-206 (miR-206) is known to regulate proliferation and is implicated in various types of cancers. However, the role of miR-206 in PAH has not been studied. In this study, it is hypothesized that miR-206 could play a role in the proliferation of PASMCs. In the present study, the expression patterns of miR-206 were investigated in normal and hypertensive mouse PASMCs. The effects of miR-206 in modulating cell proliferation, apoptosis and smooth muscle cell markers in human pulmonary artery smooth muscle cells (hPASMCs) were investigated in vitro. miR-206 expression in mouse PASMCs was correlated with an increase in right ventricular systolic pressure. Reduction of miR-206 levels in hPASMCs causes increased proliferation and reduced apoptosis and these effects were reversed by the overexpression of miR-206. miR-206 over expression also increased the levels of smooth muscle cell differentiation markers α-smooth muscle actin and calponin implicating its importance in the differentiation of SMCs. miR-206 overexpression down regulated Notch-3 expression, which is key a factor in PAH development. These results suggest that miR-206 is a potential regulator of proliferation, apoptosis and differentiation of PASMCs, and that it could be used as a novel treatment strategy in PAH.
登录
查看更多内容
影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
影响因子：
2.6
作者：
Joshi SR;McLendon JM;Comer BS;Gerthoffer WT
通讯作者：
Gerthoffer WT
影响因子：
5
作者：
Li, Lihua;Saryer, Aaron L.;Subramanian, Subbaya
通讯作者：
Subramanian, Subbaya
影响因子：
24
作者：
Humbert, M;Morrell, NW;Rabinovitch, M
通讯作者：
Rabinovitch, M
Notch 和 TGF-β 信号通路之间的串扰由 Notch 胞内结构域与 Smad3 的相互作用介导。
影响因子：
7.8
作者：
Blokzijl, A;Dahlqvist, C;Reissmann, E;Falk, A;Moliner, A;Lendahl, U;Ibáñez, CF
通讯作者：
Ibáñez, CF