TGF-beta activates Akt kinase through a microRNA-dependent amplifying circuit targeting PTEN.
作者： Mitsuo Kato , Sumanth Putta , Mei Wang , Hang Yuan , Linda Lanting
DOI: 10.1038/NCB1897
关键词:
摘要: Akt kinase is activated by transforming growth factor-beta1 (TGF-beta) in diabetic kidneys, and has important roles fibrosis, hypertrophy cell survival glomerular mesangial cells. However, the mechanisms of activation TGF-beta are not fully understood. Here we show that activates cells inducing microRNAs (miRNAs) miR-216a miR-217, both which target PTEN (phosphatase tensin homologue), an inhibitor activation. These miRNAs located within second intron a non-coding RNA (RP23-298H6.1-001). The RP23 promoter was miR-192 through E-box-regulated mechanisms, as shown previously. these miRs led to hypertrophy, were similar effects TGF-beta. studies reveal mechanism downregulation two miRs, regulated upstream Due diversity function, this miR-amplifying circuit may have key roles, only kidney disorders, but also other diseases.
nature.com
sci-hub.se 参考文章(34)
Gunter Wolf, Fuad N. Ziyadeh, Molecular mechanisms of diabetic renal hypertrophy Kidney International. ,vol. 56, pp. 393- 405 ,(1999) , 10.1046/J.1523-1755.1999.00590.X
David J. Glass, Signalling pathways that mediate skeletal muscle hypertrophy and atrophy Nature Cell Biology. ,vol. 5, pp. 87- 90 ,(2003) , 10.1038/NCB0203-87
Lee P Lim, Margaret E Glasner, Soraya Yekta, Christopher B Burge, David P Bartel, Vertebrate microRNA genes. Science. ,vol. 299, pp. 1540- 1540 ,(2003) , 10.1126/SCIENCE.1080372
Erno Wienholds, Wigard P Kloosterman, Eric Miska, Ezequiel Alvarez-Saavedra, Eugene Berezikov, Ewart De Bruijn, H Robert Horvitz, Sakari Kauppinen, Ronald HA Plasterk, MicroRNA Expression in Zebrafish Embryonic Development Science. ,vol. 309, pp. 310- 311 ,(2005) , 10.1126/SCIENCE.1114519
C. J. Braun, X. Zhang, I. Savelyeva, S. Wolff, U. M. Moll, T. Schepeler, T. F. Orntoft, C. L. Andersen, M. Dobbelstein, p53-Responsive MicroRNAs 192 and 215 Are Capable of Inducing Cell Cycle Arrest Cancer Research. ,vol. 68, pp. 10094- 10104 ,(2008) , 10.1158/0008-5472.CAN-08-1569
Jae Youn Yi, Incheol Shin, Carlos L. Arteaga, Type I Transforming Growth Factor β Receptor Binds to and Activates Phosphatidylinositol 3-Kinase Journal of Biological Chemistry. ,vol. 280, pp. 10870- 10876 ,(2005) , 10.1074/JBC.M413223200
Dan F. Lazar, Alan R. Saltiel, Lipid phosphatases as drug discovery targets for type 2 diabetes Nature Reviews Drug Discovery. ,vol. 5, pp. 333- 342 ,(2006) , 10.1038/NRD2007
Constance E. Runyan, H. William Schnaper, Anne-Christine Poncelet, The Phosphatidylinositol 3-Kinase/Akt Pathway Enhances Smad3-stimulated Mesangial Cell Collagen I Expression in Response to Transforming Growth Factor-β1 Journal of Biological Chemistry. ,vol. 279, pp. 2632- 2639 ,(2004) , 10.1074/JBC.M310412200
Giovanni Stefani, Frank J. Slack, Small non-coding RNAs in animal development Nature Reviews Molecular Cell Biology. ,vol. 9, pp. 219- 230 ,(2008) , 10.1038/NRM2347
K. Omori, L. Valiente, C. Orr, J. Rawson, K. Ferreri, I. Todorov, I. H. Al-Abdullah, S. Medicherla, A. A. Potter, G. F. Schreiner, F. Kandeel, Y. Mullen, Improvement of Human Islet Cryopreservation by a p38 MAPK Inhibitor American Journal of Transplantation. ,vol. 7, pp. 1224- 1232 ,(2007) , 10.1111/J.1600-6143.2007.01741.X