MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}
MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}
Transforming growth factor-beta (TGF-?) is a pleiotropic cytokine with important effects on processes such as fibrosis, angiogenesis, and immunosupression. Using bioinformatics, we identified SMAD2, one of the mediators of TGF-? signaling, as a predicted target for a microRNA, microRNA-155 (miR-155). MicroRNAs are a class of small non-coding RNAs that have emerged as an important class of gene expression regulators. miR-155 has been found to be involved in the regulation of the immune response in myeloid cells. Here, we provide direct evidence of binding of miR-155 to a predicted binding site and the ability of miR-155 to repress SMAD2 protein expression. We employed a lentivirally transduced monocyte cell line (THP1-155) containing an inducible miR-155 transgene to show that endogenous levels of SMAD2 protein were decreased after sustained overexpression of miR-155. This decrease in SMAD2 led to a reduction in both TGF-?-induced SMAD-2 phosphorylation and SMAD-2-dependent activation of the expression of the CAGA(12)LUC reporter plasmid. Overexpression of miR-155 altered the cellular responses to TGF-? by changing the expression of a set of genes that is involved in inflammation, fibrosis, and angiogenesis. Our study provides firm evidence of a role for miR-155 in directly repressing SMAD2 expression, and our results demonstrate the relevance of one of the two predicted target sites in SMAD2 3'-UTR. Altogether, our data uncover an important role for miR-155 in modulating the cellular response to TGF-? with possible implications in several human diseases where homeostasis of TGF-? might be altered.
gene expression, immunology, macrophage, microrna, smad transcription factor, transforming growth factor ? (tgf-?), angiogenesis, fibrosis, mir-155
41328-41336
Louafi, Fethi
75af1544-3c81-4a94-9bd3-50c2c74ad5c4
Martinez-Nunez, Rocio T.
3b2f9516-1067-4c16-90f9-e13dad821666
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
31 December 2010
Louafi, Fethi
75af1544-3c81-4a94-9bd3-50c2c74ad5c4
Martinez-Nunez, Rocio T.
3b2f9516-1067-4c16-90f9-e13dad821666
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Louafi, Fethi, Martinez-Nunez, Rocio T. and Sanchez-Elsner, Tilman
(2010)
MicroRNA-155 targets SMAD2 and modulates the response of macrophages to transforming growth factor-{beta}.
The Journal of Biological Chemistry, 285 (53), .
(doi:10.1074/jbc.M110.146852).
(PMID:21036908)
Abstract
Transforming growth factor-beta (TGF-?) is a pleiotropic cytokine with important effects on processes such as fibrosis, angiogenesis, and immunosupression. Using bioinformatics, we identified SMAD2, one of the mediators of TGF-? signaling, as a predicted target for a microRNA, microRNA-155 (miR-155). MicroRNAs are a class of small non-coding RNAs that have emerged as an important class of gene expression regulators. miR-155 has been found to be involved in the regulation of the immune response in myeloid cells. Here, we provide direct evidence of binding of miR-155 to a predicted binding site and the ability of miR-155 to repress SMAD2 protein expression. We employed a lentivirally transduced monocyte cell line (THP1-155) containing an inducible miR-155 transgene to show that endogenous levels of SMAD2 protein were decreased after sustained overexpression of miR-155. This decrease in SMAD2 led to a reduction in both TGF-?-induced SMAD-2 phosphorylation and SMAD-2-dependent activation of the expression of the CAGA(12)LUC reporter plasmid. Overexpression of miR-155 altered the cellular responses to TGF-? by changing the expression of a set of genes that is involved in inflammation, fibrosis, and angiogenesis. Our study provides firm evidence of a role for miR-155 in directly repressing SMAD2 expression, and our results demonstrate the relevance of one of the two predicted target sites in SMAD2 3'-UTR. Altogether, our data uncover an important role for miR-155 in modulating the cellular response to TGF-? with possible implications in several human diseases where homeostasis of TGF-? might be altered.
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Published date: 31 December 2010
Keywords:
gene expression, immunology, macrophage, microrna, smad transcription factor, transforming growth factor ? (tgf-?), angiogenesis, fibrosis, mir-155
Organisations:
Infection Inflammation & Immunity
Identifiers
Local EPrints ID: 181159
URI: http://eprints.soton.ac.uk/id/eprint/181159
ISSN: 0021-9258
PURE UUID: c10c4ffc-c4ed-4b86-81d3-39eb6bd121c0
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Date deposited: 14 Apr 2011 10:32
Last modified: 15 Mar 2024 03:29
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Author:
Fethi Louafi
Author:
Rocio T. Martinez-Nunez
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