MicroRNA‐24 regulates the processing of latent TGFβ1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN
- 13 October 2010
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 226 (5), 1407-1414
- https://doi.org/10.1002/jcp.22476
Abstract
Cyclic mechanical stress (CMS) leads to alterations of cellular functions in the trabecular meshwork (TM), including the up‐regulation of transforming growth factor beta 1 (TGFβ1), that can potentially contribute to the pathogenesis of glaucoma. Although microRNAs (miRNAs) are known to play important roles in many biological functions, little is known about their potential involvement in the cellular responses elicited by mechanical stress. Here we analyzed changes in miRNA expression induced by CMS, and examined the possible role of miR‐24 in the response of human TM cells to CMS. CMS induced the expression of miR‐24 that led to the down regulation of the subtilisin‐like proprotein convertase FURIN, which is known to play a major role in the processing of TGFβ1. FURIN was confirmed as a novel target of miR‐24 by 3' UTR luciferase assay and western blot. Overexpression of miR‐24 resulted in a significant decrease in activated TGFβ1. This effect was mimicked by down regulation of FURIN by siRNA. Conversely, inhibition of miR‐24 expression with a specific antagomir led to a small but significant increase in TGFβ1. Furthermore, the increase in active TGFβ1 induced by CMS in HTM cells was prevented by miR‐24. Altogether, our results suggest that miRNAs might contribute to the regulation of responses to CMS in TM cells. Specifically, miR‐24 might play an important role in modulating the induction of TGFβ1 mediated by CMS through direct targeting of FURIN. J. Cell. Physiol. 226: 1407–1414, 2011.Keywords
This publication has 71 references indexed in Scilit:
- MiR-21 is induced in endothelial cells by shear stress and modulates apoptosis and eNOS activityBiochemical and Biophysical Research Communications, 2010
- MicroRNAs Regulate Human Hepatocyte Nuclear Factor 4α, Modulating the Expression of Metabolic Enzymes and Cell CyclePublished by Elsevier BV ,2010
- MicroRNA-19a mediates the suppressive effect of laminar flow on cyclin D1 expression in human umbilical vein endothelial cellsProceedings of the National Academy of Sciences of the United States of America, 2010
- The EMBO Journal, 2009
- Simultaneous Transforming Growth Factor β-Tumor Necrosis Factor Activation and Cross-talk Cause Aberrant Remodeling Response and Myocardial Fibrosis in Timp3-deficient HeartPublished by Elsevier BV ,2009
- miR-24 Inhibits Cell Proliferation by Targeting E2F2, MYC, and Other Cell-Cycle Genes via Binding to “Seedless” 3′UTR MicroRNA Recognition ElementsMolecular Cell, 2009
- The changing paradigm of outflow resistance generation: Towards synergistic models of the JCT and inner wall endotheliumExperimental Eye Research, 2009
- miR-24–mediated downregulation of H2AX suppresses DNA repair in terminally differentiated blood cellsNature Structural & Molecular Biology, 2009
- MicroRNA-21 protects against the H2O2-induced injury on cardiac myocytes via its target gene PDCD4Journal of Molecular and Cellular Cardiology, 2009
- Extracellular matrix in the trabecular meshworkExperimental Eye Research, 2008