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首页> 外文期刊>BMC Molecular Biology >MKL1 inhibits cell cycle progression through p21 in podocytes
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MKL1 inhibits cell cycle progression through p21 in podocytes

机译：MKL1通过足细胞中的p21抑制细胞周期进程

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摘要

The glomerular podocyte is a highly specialized cell type with the ability to ultrafilter blood and support glomerular capillary pressure. However, little is known about the genetic programs leading to this functionality or the final phenotype. In the current study, we found that the expression of a myocardin/MKL family member, MKL1, was significantly upregulated during cell cycle arrest induced by a temperature switch in murine podocyte clone 5 (MPC5) cells. Further investigation demonstrated that overexpression of MKL1 led to inhibition of cell proliferation by decreasing the number of cells in S phase of the cell cycle. In contrast, MKL1 knockdown by RNA interference had the opposite effect, highlighting a potential role of MKL1 in blocking G1/S transition of the cell cycle in MPC5 cells. Additionally, using an RT2 Profiler PCR Array, p21 was identified as a direct target of MKL1. We further revealed that MKL1 activated p21 transcription by recruitment to the CArG element in its promoter, thus resulting in cell cycle arrest. In addition, the expression of MKL1 is positively correlated with that of p21 in podocytes in postnatal mouse kidney and significantly upregulated during the morphological switch of podocytes from proliferation to differentiation. Our observations demonstrate that MKL1 has physiological roles in the maturation and development of podocytes, and thus its misregulation might lead to glomerular and renal dysfunction.
机译：肾小球足细胞是高度专业化的细胞类型，具有超滤血液和支持肾小球毛细血管压力的能力。但是，对于导致这种功能或最终表型的遗传程序知之甚少。在当前的研究中，我们发现在小鼠足细胞克隆5（MPC5）细胞中，温度切换诱导的细胞周期停滞期间，心肌素/ MKL家族成员MKL1的表达明显上调。进一步的研究表明，MKL1的过表达通过减少细胞周期S期的细胞数来抑制细胞增殖。相反，RNA干扰引起的MKL1抑制具有相反的作用，突显了MKL1在阻止MPC5细胞中细胞周期的G1 / S转变中的潜在作用。此外，使用RT2 Profiler PCR阵列，p21被鉴定为MKL1的直接靶标。我们进一步揭示，MKL1通过募集其启动子中的CArG元件来激活p21转录，从而导致细胞周期停滞。此外，MKL1的表达与小鼠肾脏足细胞中p21的表达正相关，并且在足细胞从增殖到分化的形态转换过程中显着上调。我们的观察表明，MKL1在足细胞的成熟和发育中具有生理作用，因此其失调可能导致肾小球和肾功能异常。

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