MKL1 inhibits cell cycle progression through p21 in podocytes.
MKL1 inhibits cell cycle progression through p21 in podocytes.
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MKL1 通过足细胞中的 p21 抑制细胞周期进程。
DOI：
10.1186/s12867-015-0029-5
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发表时间：
2015-02-12
影响因子：
--
通讯作者：
Yang Z
中科院分区：
文献类型：
--
作者：
Yang S;Liu L;Xu P;Yang Z
肾小球足细胞是一种高度特化的细胞类型，具有超滤血液和支持肾小球毛细血管压力的能力。然而，对于导致这种功能或最终表型的遗传程序知之甚少。在目前的研究中，我们发现在温度开关诱导的小鼠足细胞克隆5 （MPC5）细胞周期阻滞中，心肌素/MKL家族成员MKL1的表达显著上调。进一步的研究表明，过表达MKL1通过减少细胞周期S期的细胞数量来抑制细胞增殖。相比之下，通过RNA干扰敲低MKL1具有相反的作用，突出了MKL1在阻断MPC5细胞G1/S细胞周期转变中的潜在作用。此外，使用RT2 Profiler PCR阵列，p21被确定为MKL1的直接靶点。我们进一步发现MKL1通过招募启动子中的CArG元件激活p21转录，从而导致细胞周期阻滞。此外，MKL1的表达与p21在出生后小鼠肾足细胞中的表达呈正相关，并在足细胞从增殖到分化的形态转换过程中显著上调。我们的观察结果表明，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脏功能障碍。本文的在线版本（doi:10.1186/s12867-015-0029-5）包含补充材料，仅供授权用户使用。
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. The online version of this article (doi:10.1186/s12867-015-0029-5) contains supplementary material, which is available to authorized users.
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