Myocardial connexin-43 and PKC signalling are involved in adaptation of the heart to irradiation-induced injury: Implication of miR-1 and miR-21
Myocardial connexin-43 and PKC signalling are involved in adaptation of the heart to irradiation-induced injury: Implication of miR-1 and miR-21
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DOI：
10.4149/gpb_2015038
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发表时间：
2016-04-01
影响因子：
1.5
通讯作者：
Tribulova, Narcis
中科院分区：
文献类型：
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作者：
Viczenczova, Csilla;Bacova, Barbara Szeiffova;Tribulova, Narcis
细胞间连接蛋白-43(Cx43)通道是电耦合和直接心肌细胞间通讯以确保心脏功能所必需的。Cx43的表达会因应激条件而改变，也会受到细胞外基质改变的影响。本研究旨在探讨胸部照射对心肌Cx43及其调控基因GJA1转录的miR-1和Cx43表达的影响。还研究了miR-21调节细胞外基质蛋白的表达和可能影响Cx43介导的偶联的PKC信号的意义。Western印迹和实时荧光定量聚合酶链式反应分析显示，健康Wistar大鼠胸部单纯照射25Gy6周后，心肌组织发生明显改变：1)总Cx43蛋白表达及其功能磷酸化形式增加，2)抑制miR-1的表达，3)使Cx43磷酸化的PKC epsilon表达增强，4)miR-21水平升高，5)PKC表达增加。这些结果表明，辐射可能通过miR-21和PKC信号通路引起miR-1对心肌Cx43表达的转录后调控。我们的结论是，单次照射有可能增强心肌细胞间的通讯，这可能对心脏有益，这需要在进一步的研究中进行详细的研究。
Intercellular connexin-43 (Cx43) channels are essential for electrical coupling and direct cardiac cell to cell communication to ensure heart function. Expression of Cx43 is altered due to stressful conditions and also affected by the alterations in extracellular matrix. We aimed to explore the effect of chest irradiation on myocardial expression of Cx43 and miR-1 which regulates GJA1 gene transcription for Cx43. Implication of miR-21 that regulates expression of extracellular matrix proteins and PKC signalling that may affect Cx43-mediated coupling was examined as well. Western blot and real-time PCR analyses revealed that six weeks after the exposure of healthy Wistar rats chest to single irradiation of 25 Gy significant myocardial alterations were observed: 1) increase of total Cx43 protein expression and its functional phosphorylated forms; 2) suppressed levels of miR-1; 3) enhanced expression of PKC epsilon which phosphorylates Cx43; 4) increase of miR-21 levels; 5) increase of PKC expression. These results suggest that irradiation causes post-transcriptional regulation of myocardial Cx43 expression by miR-1 possibly through miR-21 and PKC signalling. We conclude that single dose of irradiation has the potential to enhance myocardial intercellular communication that might be beneficial for the heart that needs to be investigated in details in further studies.