title: MKL1 inhibits cell cycle progression through p21 in podocytes.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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 RT(2) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical School, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, 94 Weijin Road, Tianjin, 300071, China. yangshuang@nankai.edu.cn.
authors.forename: Shuang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Medical School, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, 94 Weijin Road, Tianjin, 300071, China. 370814309@qq.com.
authors.forename: Lingjia
authors.initials: L
authors.lastname: Liu
authors.affiliation: Tianjin University of Traditional Chinese Medicine, Tianjin, 300193, China. 309632734@qq.com.
authors.forename: Pengjuan
authors.initials: P
authors.lastname: Xu
authors.affiliation: Medical School, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, 94 Weijin Road, Tianjin, 300071, China. zhuoyang@nankai.edu.cn.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D055785:Gene Knockdown Techniques; D051379:Mice; D050199:Podocytes / Q000166:cytology / Q000502:physiology*; D013696:Temperature; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D015854:Up-Regulation
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; C511173:Mrtfa protein, mouse; D015534:Trans-Activators