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Downregulation of the ERK 1 and 2 mitogen activated protein kinases using antisense oligonucleotides inhibits proliferation of porcine vascular smooth muscle cells

Downregulation of the ERK 1 and 2 mitogen activated protein kinases using antisense oligonucleotides inhibits proliferation of porcine vascular smooth muscle cells
Downregulation of the ERK 1 and 2 mitogen activated protein kinases using antisense oligonucleotides inhibits proliferation of porcine vascular smooth muscle cells
The current model of the arterial response to injury suggests that proliferation of vascular smooth muscle cells is a central event. Mitogen activated protein kinases are part of the final common pathway of intracellular signalling involved in cell division and thus constitute an attractive target in attempting to inhibit this proliferation. We hypothesised that antisense oligonucleotides to mitogen activated protein kinase would inhibit serum induced smooth muscle cell proliferation by downregulating the protein. Porcine vascular smooth muscle cells were cultured and an antisense oligonucleotide sequence against the ERK family of mitogen activated protein kinases (AMK1) was introduced by liposomal transfection. Sense oligonucleotides and a random sequence were used as controls. Proliferation was inhibited by AMK1 versus the sense controls, as assessed by tritiated thymidine incorporation (P<0.01). Immunoblots revealed downregulation of the target protein by AMK1 by 63% versus the sense control (P<0.05). In conclusion, antisense oligonucleotides specifically inhibited proliferation and downregulated the target protein. This is consistent with a central role for mitogen activated protein kinases in vascular smooth muscle cell proliferation in the porcine model. In addition, the data suggest a possible role for antisense oligonucleotides in the modulation of the arterial injury response.
0021-9150
289-295
Fisher, M.
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Liu, B.
c99d0f80-7480-4069-a77c-0e79c622e9e4
Glennon, P.E.
59203826-d82c-460e-add0-0af4b0948d01
Southgate, K.M.
a1cb8424-2aeb-41f4-88fb-ff6743ddd0ab
Sale, E.M.
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Sale, G.J.
9da2ccd1-1a75-42e8-8c55-5bdfef6ccd10
Lewis, M.J.
12db686f-b8a2-415f-92bd-2fa922605de5
Groves, P.H.
506165af-4970-47bc-833f-5e46e73f5ebb
Fisher, M.
1ba6a9e9-9021-4c95-8423-4f04c52b6f9e
Liu, B.
c99d0f80-7480-4069-a77c-0e79c622e9e4
Glennon, P.E.
59203826-d82c-460e-add0-0af4b0948d01
Southgate, K.M.
a1cb8424-2aeb-41f4-88fb-ff6743ddd0ab
Sale, E.M.
6cb82c59-6168-403d-8703-7000728c8584
Sale, G.J.
9da2ccd1-1a75-42e8-8c55-5bdfef6ccd10
Lewis, M.J.
12db686f-b8a2-415f-92bd-2fa922605de5
Groves, P.H.
506165af-4970-47bc-833f-5e46e73f5ebb

Fisher, M., Liu, B., Glennon, P.E., Southgate, K.M., Sale, E.M., Sale, G.J., Lewis, M.J. and Groves, P.H. (2001) Downregulation of the ERK 1 and 2 mitogen activated protein kinases using antisense oligonucleotides inhibits proliferation of porcine vascular smooth muscle cells. Atherosclerosis, 156 (2), 289-295.

Record type: Article

Abstract

The current model of the arterial response to injury suggests that proliferation of vascular smooth muscle cells is a central event. Mitogen activated protein kinases are part of the final common pathway of intracellular signalling involved in cell division and thus constitute an attractive target in attempting to inhibit this proliferation. We hypothesised that antisense oligonucleotides to mitogen activated protein kinase would inhibit serum induced smooth muscle cell proliferation by downregulating the protein. Porcine vascular smooth muscle cells were cultured and an antisense oligonucleotide sequence against the ERK family of mitogen activated protein kinases (AMK1) was introduced by liposomal transfection. Sense oligonucleotides and a random sequence were used as controls. Proliferation was inhibited by AMK1 versus the sense controls, as assessed by tritiated thymidine incorporation (P<0.01). Immunoblots revealed downregulation of the target protein by AMK1 by 63% versus the sense control (P<0.05). In conclusion, antisense oligonucleotides specifically inhibited proliferation and downregulated the target protein. This is consistent with a central role for mitogen activated protein kinases in vascular smooth muscle cell proliferation in the porcine model. In addition, the data suggest a possible role for antisense oligonucleotides in the modulation of the arterial injury response.

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Published date: 1 June 2001

Identifiers

Local EPrints ID: 56149
URI: http://eprints.soton.ac.uk/id/eprint/56149
ISSN: 0021-9150
PURE UUID: e709036a-ea72-4a06-baa3-23195aa670e5

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Date deposited: 07 Aug 2008
Last modified: 08 Jan 2022 16:01

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Contributors

Author: M. Fisher
Author: B. Liu
Author: P.E. Glennon
Author: K.M. Southgate
Author: E.M. Sale
Author: G.J. Sale
Author: M.J. Lewis
Author: P.H. Groves

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