College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Nankai University, Tianjin, 300071, China.
College of Medicine, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials for Ministry of Education, Nankai University, Tianjin, 300071, China; Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, 06510, USA.
Arch Biochem Biophys. 2018 Sep 1;653:80-89. doi: 10.1016/j.abb.2018.06.013. Epub 2018 Jun 27.
Transient receptor potential canonical 6 (TRPC6) and large-conductance Ca-activated K channels (BK), two of the key ion channels for blood filtration function of podocytes, have been implicated in the pathogenesis of kidney diseases. Moreover, it has been reported that miR-200 b plays an important role in regulating the biological processes of podocytes. In this study, we aimed to examine whether there was a relationship between miR-200 b-3p and the two ion channels. It was suggested that miR-200 b-3p down-regulation inhibited the currents of TRPC6 and BK channels. It also showed that miR-200 b-3p inhibition reduced the levels of protein expression and mRNA transcription of TRPC6 and BK channels. Moreover, the down-regulation of miR-200 b-3p resulted in the decrease of the intracellular Ca concentration. It was also suggested that the decrease of BK currents resulting from miR-200 b-3p inhibition could be regulated by TRPC6 channels. TRPC6 blockage also inhibited BK currents and reduced the level of BK expression. These results together suggested that miR-200 b-3p inhibition reduced the currents of TRPC6, which led to the decrease of intracellular Ca concentration. The decrease of Ca source required for BK activation may result in the inhibition of BK currents.
瞬时受体电位经典型 6 型（TRPC6）和大电导钙激活钾通道（BK）是足细胞滤过功能的关键离子通道之一，与肾脏疾病的发病机制有关。此外，有研究报道 miR-200b 在调节足细胞的生物学过程中起着重要作用。在本研究中，我们旨在研究 miR-200b-3p 是否与这两种离子通道有关。结果表明，miR-200b-3p 的下调抑制了 TRPC6 和 BK 通道的电流。此外，miR-200b-3p 的抑制降低了 TRPC6 和 BK 通道的蛋白表达和 mRNA 转录水平。此外，miR-200b-3p 的下调导致细胞内 Ca 浓度降低。还表明，miR-200b-3p 抑制引起的 BK 电流减少可通过 TRPC6 通道调节。TRPC6 阻断也抑制 BK 电流并降低 BK 表达水平。这些结果共同表明，miR-200b-3p 的抑制降低了 TRPC6 的电流，从而导致细胞内 Ca 浓度降低。激活 BK 所需的 Ca 源减少可能导致 BK 电流抑制。
