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Abstract #27874 Published in IGR 13-1
MicroRNA-24 regulates the processing of latent TGF(beta)1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN
Luna C; Li G; Qiu J; Epstein DL; Gonzalez PJournal of Cellular Physiology 2011; 226: 1407-1414
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 (TGF(beta)1), 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 TGF(beta)1. 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 TGF(beta)1. 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 TGF(beta)1. Furthermore, the increase in active TGF(beta)1 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 TGF(beta)1 mediated by CMS through direct targeting of FURIN. (copyright) 2010 Wiley-Liss, Inc.
P. Gonzalez. Duke University, PO Box 3802, Durham, NC 27710, United States. gonza012@mc.duke.edu
Classification:
2.5.1 Trabecular meshwork (Part of: 2 Anatomical structures in glaucoma > 2.5 Meshwork)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)
3.9 Pathophysiology (Part of: 3 Laboratory methods)
3.6 Cellular biology (Part of: 3 Laboratory methods)