MKL1 inhibits cell cycle progression through p21 in podocytes

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• 作者：Shuang Yang (1)
  Lingjia Liu (1)
  Pengjuan Xu (2)
  Zhuo Yang (1)
  
  1. Medical School ; Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation ; Nankai University ; 94 Weijin Road ; Tianjin ; 300071 ; China
  2. Tianjin University of Traditional Chinese Medicine ; Tianjin ; 300193 ; China
  
• 关键词：Kidney development ; Podocyte ; Cell growth arrest ; MKL1
• 刊名：BMC Molecular Biology
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：16
• 期：1
• 全文大小：3,799 KB
• 参考文献：1. Pavenst盲dt H, Kriz W, Kretzler M. Cell biology of the glomerular podocyte. Physiol Rev. 2003;83(1):253鈥?07.
  2. Greka A, Mundel P. Cell biology and pathology of podocytes. Annu Rev Physiol. 2012;74:299鈥?23. CrossRef
  3. Kreidberg JA. Podocyte differentiation and glomerulogenesis. J Am Soc Nephrol. 2003;14(3):806鈥?4. CrossRef
  4. Kobayashi N, Gao SY, Chen J, Saito K, Miyawaki K, Li CY, et al. Process formation of the renal glomerular podocyte: is there common molecular machinery for processes of podocytes and neurons? Anat Sci Int. 2004;79(1):1鈥?0. CrossRef
  5. Marshall CB, Shankland SJ. Cell cycle regulatory proteins in podocyte health and disease. Nephron Exp Nephrol. 2007;106(2):e51鈥?. CrossRef
  6. Price PM. A role for novel cell-cycle proteins in podocyte biology. Kidney Int. 2010;77(8):660鈥?. CrossRef
  7. Kriz W, Shirato I, Nagata M, LeHir M, Lemley KV. The podocyte鈥檚 response to stress: the enigma of foot process effacement. Am J Physiol Renal Physiol. 2013;304(4):F333鈥?7. CrossRef
  8. Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, et al. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet. 2001;28(3):220鈥?. CrossRef
  9. Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, et al. Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acutemegakaryocytic leukemia. Proc Natl Acad Sci U S A. 2001;98(10):5776鈥?. CrossRef
  10. Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, et al. Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor. Cell. 2001;105(7):851鈥?2. CrossRef
  11. Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, et al. Potentiation of serum response factor activity by a family of myocardin-related transcription factors. Proc Natl Acad Sci U S A. 2002;99(23):14855鈥?0. CrossRef
  12. Cen B, Selvaraj A, Burgess RC, Hitzler JK, Ma Z, Morris SW, et al. Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required forserum induction of SRF target genes. Mol Cell Biol. 2003;23(18):6597鈥?08. CrossRef
  13. Selvaraj A, Prywes R. Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent. BMC Mol Biol. 2004;5:13. CrossRef
  14. Wang Z, Wang DZ, Pipes GC, Olson EN. Myocardin is a master regulator of smooth muscle gene expression. Proc Natl Acad Sci U S A. 2003;100(12):7129鈥?4. CrossRef
  15. Yoshida T, Sinha S, Dandr茅 F, Wamhoff BR, Hoofnagle MH, Kremer BE, et al. Myocardin is a key regulator of CArG-dependent transcription of multiple smooth muscle marker genes. Circ Res. 2003;92(8):856鈥?4. CrossRef
  16. Chen J, Kitchen CM, Streb JW, Miano JM. Myocardin: a component of a molecular switch for smooth muscle differentiation. J Mol Cell Cardiol. 2002;34(10):1345鈥?6. CrossRef
  17. Selvaraj A, Prywes R. Megakaryoblastic leukemia-1/2, a transcriptional co-activator of serum response factor, is required for skeletal myogenic differentiation. J Biol Chem. 2003;278(43):41977鈥?7. CrossRef
  18. Parmacek MS. Myocardin-related transcription factors: critical coactivators regulating cardiovascular development and adaptation. Circ Res. 2007;100(5):633鈥?4. CrossRef
  19. Mokalled MH, Johnson A, Kim Y, Oh J, Olson EN. Myocardin-related transcription factors regulate the Cdk5/Pctaire1 kinase cascade to control neurite outgrowth, neuronal migration and brain development. Development. 2010;137(14):2365鈥?4. CrossRef
  20. Ly DL, Waheed F, Lodyga M, Speight P, Masszi A, Nakano H, et al. Hyperosmotic stress regulates the distribution and stability of myocardin-related transcription factor, a key modulator of the cytoskeleton. Am J Physiol Cell Physiol. 2013;304(2):C115鈥?7. CrossRef
  21. Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, et al. Role for MKL1 in megakaryocytic maturation. Blood. 2009;113(12):2826鈥?4. CrossRef
  22. Smith EC, Teixeira AM, Chen RC, Wang L, Gao Y, Hahn KL, et al. Induction of megakaryocyte differentiation drives nuclear accumulation and transcriptional function of MKL1 via actin polymerization and RhoA activation. Blood. 2013;121(7):1094鈥?01. CrossRef
  23. Fan L, Sebe A, P茅terfi Z, Masszi A, Thirone AC, Rotstein OD, et al. Cell contact-dependent regulation of epithelial-myofibroblast transition via the rho-rho kinase-phospho-myosin pathway. Mol Biol Cell. 2007;18(3):1083鈥?7. CrossRef
  24. Elberg G, Chen L, Elberg D, Chan MD, Logan CJ, Turman MA. MKL1 mediates TGF-beta1-induced alpha-smooth muscle actin expression in human renal epithelial cells. Am J Physiol Renal Physiol. 2008;294(5):F1116鈥?8. CrossRef
  25. Mihira H, Suzuki HI, Akatsu Y, Yoshimatsu Y, Igarashi T, Miyazono K, et al. TGF-尾-induced mesenchymal transition of MS-1 endothelial cells requires Smad-dependent cooperative activation of Rho signals and MRTF-A. J Biochem. 2012;151(2):145鈥?6. CrossRef
  26. Descot A, Hoffmann R, Shaposhnikov D, Reschke M, Ullrich A, Posern G. Negative regulation of the EGFR-MAPK cascade by actin-MAL-mediated Mig6/Errfi-1 induction. Mol Cell. 2009;35(3):291鈥?04. CrossRef
  27. Kimura Y, Morita T, Hayashi K, Miki T, Sobue K. Myocardin functions as an effective inducer of growth arrest and differentiation in human uterine leiomyosarcoma cells. Cancer Res. 2010;70(2):501鈥?1. CrossRef
  28. Tang RH, Zheng XL, Callis TE, Stansfield WE, He J, Baldwin AS, et al. Myocardin inhibits cellular proliferation by inhibiting NF-kappaB(p65)-dependent cell cycle progression. Proc Natl Acad Sci U S A. 2008;105(9):3362鈥?. CrossRef
  29. Saleem MA, O'Hare MJ, Reiser J, Coward RJ, Inward CD, Farren T, et al. A conditionally immortalized human podocyte cell line demonstrating nephrin and podocin expression. J Am Soc Nephrol. 2002;13(3):630鈥?.
  30. Jeon ES, Park WS, Lee MJ, Kim YM, Han J, Kim JH. A Rho kinase/myocardin-related transcription factor-A-dependent mechanism underlies the sphingosylphosphorylcholine-induced differentiation of mesenchymal stem cells into contractile smooth musclecells. Circ Res. 2008;103(6):635鈥?2. CrossRef
  31. Velasquez LS, Sutherland LB, Liu Z, Grinnell F, Kamm KE, Schneider JW, et al. Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiationand wound healing. Proc Natl Acad Sci U S A. 2013;110(42):16850鈥?. CrossRef
  32. Nobusue H, Onishi N, Shimizu T, Sugihara E, Oki Y, Sumikawa Y, et al. Regulation of MKL1 via actin cytoskeleton dynamics drives adipocyte differentiation. Nat Commun. 2014;5:3368. CrossRef
  33. Shaposhnikov D, Descot A, Schilling J, Posern G. Myocardin-related transcription factor A regulates expression of Bok and Noxa and is involved in apoptotic signaling. Cell Cycle. 2012;11(1):141鈥?0. CrossRef
  34. Milyavsky M, Shats I, Cholostoy A, Brosh R, Buganim Y, Weisz L, et al. Inactivation of myocardin and p16 during malignant transformation contributes to a differentiation defect. Cancer Cell. 2007;11(2):133鈥?6. CrossRef
  35. Shaposhnikov D, Kuffer C, Storchova Z, Posern G. Myocardin related transcription factors are required for coordinated cell cycle progression. Cell Cycle. 2013;12(11):1762鈥?2. CrossRef
  36. Barisoni L, Mokrzycki M, Sablay L, Nagata M, Yamase H, Mundel P. Podocyte cell cycle regulation and proliferation in collapsing glomerulopathies. Kidney Int. 2000;58(1):137鈥?3. CrossRef
  37. Wang S, Kim JH, Moon KC, Hong HK, Lee HS. Cell-cycle mechanisms involved in podocyte proliferation in cellular lesion of focal segmental glomerulosclerosis. Am J Kidney Dis. 2004;43(1):19鈥?7. CrossRef
  38. Srivastava T, Garola RE, Whiting JM, Alon US. Cell-cycle regulatory proteins in podocyte cell in idiopathic nephrotic syndrome of childhood. Kidney Int. 2003;63(4):1374鈥?1. CrossRef
  39. Shankland SJ, Floege J, Thomas SE, Nangaku M, Hugo C, Pippin J, et al. Cyclin kinase inhibitors are increased during experimental membranous nephropathy: potential role in limiting glomerular epithelial cell proliferation in vivo. Kidney Int. 1997;52(2):404鈥?3. CrossRef
  40. Hoshi S, Shu Y, Yoshida F, Inagaki T, Sonoda J, Watanabe T, et al. Podocyte injury promotes progressive nephropathy in zucker diabetic fatty rats. Lab Invest. 2002;82(1):25鈥?5. CrossRef
  41. Nitta K, Horita S, Honda K, Uchida K, Watanabe T, Nihei H, et al. Glomerular expression of cell-cycle-regulatory proteins in human crescentic glomerulonephritis. Virchows Arch. 1999;435(4):422鈥?. CrossRef
  42. Xu H, Wu X, Qin H, Tian W, Chen J, Sun L, et al. Myocardin-Related Transcription Factor A Epigenetically Regulates Renal Fibrosis in Diabetic Nephropathy. J Am Soc Nephrol. 2014; [Epub ahead of print].
  43. Fintha A, Gasparics 脕, Fang L, Erdei Z, Hamar P, M贸zes MM, et al. Characterization and role of SCAI during renal fibrosis and epithelial-to-mesenchymal transition. Am J Pathol. 2013;182(2):388鈥?00. CrossRef
  44. Yang S, Du J, Wang Z, Yuan W, Qiao Y, Zhang M, et al. BMP-6 promotes E-cadherin expression through repressing deltaEF1 in breast cancer cells. BMC Cancer. 2007;7:211. CrossRef
  
• 刊物主题：Biochemistry, general; Nucleic Acid Chemistry;
• 出版者：BioMed Central
• ISSN：1471-2199

文摘

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 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. 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.