PDGFBB promotes proliferation and migration via regulating miR-1181/STAT3 axis in human pulmonary arterial smooth muscle cells
PDGFBB promotes proliferation and migration via regulating miR-1181/STAT3 axis in human pulmonary arterial smooth muscle cells
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PDGFBB 通过调节人肺动脉平滑肌细胞中的 miR-1181/STAT3 轴促进增殖和迁移。
DOI：
10.1152/ajplung.00224.2018
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发表时间：
2018-12-01
影响因子：
4.9
通讯作者：
Gou, Deming
中科院分区：
文献类型：
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作者：
Qian, Zhengjiang;Li, Yanjiao;Gou, Deming
血小板源性生长因子（PDGF）可诱导肺动脉平滑肌细胞（PASMCs）过度增殖，是肺动脉高压（PAH）发生、发展的关键因素。我们先前发现miR-1181在人PASMCs中被PDGFBB显著下调。在这项工作中，我们进一步探讨了miR-1181在PDGF诱导的PASMCs中的功能和潜在的调控机制。首先，在PDGFBB处理下表征miR-1181的表达模式，并且发现PDGF受体/PKC β信号传导抑制miR-1181表达。然后，分别进行了功能获得和功能丧失实验，并揭示了miR-1181在抑制PASMC增殖和迁移中的突出作用。流式细胞仪分析表明，miR-1181通过影响PASMC从G 0/G1期向S期的转换，从而调控PASMC的增殖。此外，我们发现靶向STAT 3的miR-1181形成了调节PASMC增殖的调节轴。最后，在PAH成人和新生儿患者中也观察到血清miR-1181表达降低。总之，本研究提供了新的发现，即miR-1181/STAT 3轴介导PIXWBB诱导的人PASMCs功能障碍，这意味着miR-1181作为血管重塑疾病的治疗和诊断候选物的潜在用途。
Platelet-derived growth factor (PDGF) can induce hyperproliferation of pulmonary artery smooth muscle cells (PASMCs), which is a key causative factor to the occurrence and progression of pulmonary arterial hypertension (PAH). We previously identified that miR-1181 is significantly down-regulated by PDGFBB in human PASMCs. In this work, we further explore the function of miR-1181 and underlying regulatory mechanisms in PDGF-induced PASMCs. First, the expression pattern of miR-1181 was characterized under PDGFBB treatment, and PDGF receptor/PKC beta signaling was found to repress miR-1181 expression. Then, gain- and loss-of-function experiments were respectively conducted and revealed the prominent role of miR-1181 in inhibiting PASMC proliferation and migration. Flow cytometry analysis suggested that miR-1181 regulated the PASMC proliferation through influencing the cell cycle transition from G0/G1 to S phase. Moreover, we exhibited that miR-1181 targeting STAT3 formed a regulatory axis to modulate PASMC proliferation. Finally, serum miR-1181 expression was also observed to be reduced in adult and newborn patients with PAH. Overall, this study provides novel findings that the miR-1181/STAT3 axis mediated PIXWBB-induced dysfunction in human PASMCs, implying a potential use of miR-1181 as a therapeutic and diagnostic candidate for the vascular remodeling diseases.