Angiotensin II-induced smooth muscle cell migration is mediated by LDL receptor-related protein 1 via regulation of matrix metalloproteinase 2 expression

Hae Ok Jung; Jae Sun Uhm; Suk Min Seo; Jee Hee Kim; Ho Joong Youn; Sang Hong Baek; Wook Sung Chung; Ki Bae Seung

doi:10.1016/j.bbrc.2010.10.019

Angiotensin II-induced smooth muscle cell migration is mediated by LDL receptor-related protein 1 via regulation of matrix metalloproteinase 2 expression

Hae Ok Jung, Jae Sun Uhm, Suk Min Seo, Jee Hee Kim, Ho Joong Youn, Sang Hong Baek, Wook Sung Chung, Ki Bae Seung

Catholic Univ. of Korea Coll. Med.

Research output: Contribution to journal › Article › peer-review

15 Scopus citations

Abstract

Angiotensin II (Ang II), one of the main vasoactive hormones of the renin-angiotensin system, contributes to the development and progression of atherosclerosis by inducing vascular smooth muscle cells (VSMCs) migration. Although previous studies have shown that Ang II upregulates low density lipoprotein receptor-related protein 1 (LRP1) expression in VSMCs and increases VSMCs migration, the role of LRP1 in Ang II-induced VSMCs migration remains unclear. Here, we reveal a novel mechanism by which LRP1 induces the expression of matrix metalloproteinase 2 (MMP2) and thereby promotes the migration of rat aortic SMCs (RAoSMCs). Knockdown of LRP1 expression greatly decreased RAoSMCs migration, which was rescued by forced expression of a functional LRP1 minireceptor, suggesting that LRP1 is a key regulator of Ang II-induced RAoSMCs migration. Inhibition of ligand binding to LRP1 by the specific antagonist receptor-associated protein (RAP) also led to reduced RAoSMCs migration. Because MMPs play critical roles in RAoSMCs migration, we examined the expression of several MMPs and found that the expression of functional MMP2 was selectively increased by Ang II treatment and decreased in LRP1-knockdown RAoSMCs. More interestingly, reduced MMP2 expression in LRP1-knockdown cells was completely rescued by exogenous expression of mLRP4, suggesting that MMP2 is a downstream regulator of LRP1 in Ang II-induced RAoSMCs migration. Together, our data strongly suggest that LRP1 promotes the migration of RAoSMCs by regulating the expression and function of MMP2.

Original language	English
Pages (from-to)	577-582
Number of pages	6
Journal	Biochemical and Biophysical Research Communications
Volume	402
Issue number	4
DOIs	https://doi.org/10.1016/j.bbrc.2010.10.019
State	Published - 26 Nov 2010

Bibliographical note

Funding Information:
This research was supported by Seoul St. Mary’s Clinical Medicine Research Program year of 2009 through the Catholic University of Korea. Anti-LRP1 IgG, human recombinant receptor-associated protein (RAP), minireceptor of LRP1 mLRP4, and MMP2 and MMP9 promoter luciferase vectors were kindly provided by Dr. Heesang Song.

Keywords

Angiotensin II
LRP1
Matrix metalloproteinase 2
Migration
Smooth muscle cells

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10.1016/j.bbrc.2010.10.019

Cite this

Jung, H. O., Uhm, J. S., Seo, S. M., Kim, J. H., Youn, H. J., Baek, S. H., Chung, W. S., & Seung, K. B. (2010). Angiotensin II-induced smooth muscle cell migration is mediated by LDL receptor-related protein 1 via regulation of matrix metalloproteinase 2 expression. Biochemical and Biophysical Research Communications, 402(4), 577-582. https://doi.org/10.1016/j.bbrc.2010.10.019

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title = "Angiotensin II-induced smooth muscle cell migration is mediated by LDL receptor-related protein 1 via regulation of matrix metalloproteinase 2 expression",

abstract = "Angiotensin II (Ang II), one of the main vasoactive hormones of the renin-angiotensin system, contributes to the development and progression of atherosclerosis by inducing vascular smooth muscle cells (VSMCs) migration. Although previous studies have shown that Ang II upregulates low density lipoprotein receptor-related protein 1 (LRP1) expression in VSMCs and increases VSMCs migration, the role of LRP1 in Ang II-induced VSMCs migration remains unclear. Here, we reveal a novel mechanism by which LRP1 induces the expression of matrix metalloproteinase 2 (MMP2) and thereby promotes the migration of rat aortic SMCs (RAoSMCs). Knockdown of LRP1 expression greatly decreased RAoSMCs migration, which was rescued by forced expression of a functional LRP1 minireceptor, suggesting that LRP1 is a key regulator of Ang II-induced RAoSMCs migration. Inhibition of ligand binding to LRP1 by the specific antagonist receptor-associated protein (RAP) also led to reduced RAoSMCs migration. Because MMPs play critical roles in RAoSMCs migration, we examined the expression of several MMPs and found that the expression of functional MMP2 was selectively increased by Ang II treatment and decreased in LRP1-knockdown RAoSMCs. More interestingly, reduced MMP2 expression in LRP1-knockdown cells was completely rescued by exogenous expression of mLRP4, suggesting that MMP2 is a downstream regulator of LRP1 in Ang II-induced RAoSMCs migration. Together, our data strongly suggest that LRP1 promotes the migration of RAoSMCs by regulating the expression and function of MMP2.",

keywords = "Angiotensin II, LRP1, Matrix metalloproteinase 2, Migration, Smooth muscle cells",

author = "Jung, {Hae Ok} and Uhm, {Jae Sun} and Seo, {Suk Min} and Kim, {Jee Hee} and Youn, {Ho Joong} and Baek, {Sang Hong} and Chung, {Wook Sung} and Seung, {Ki Bae}",

note = "Funding Information: This research was supported by Seoul St. Mary{\textquoteright}s Clinical Medicine Research Program year of 2009 through the Catholic University of Korea. Anti-LRP1 IgG, human recombinant receptor-associated protein (RAP), minireceptor of LRP1 mLRP4, and MMP2 and MMP9 promoter luciferase vectors were kindly provided by Dr. Heesang Song.",

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Angiotensin II-induced smooth muscle cell migration is mediated by LDL receptor-related protein 1 via regulation of matrix metalloproteinase 2 expression. / Jung, Hae Ok; Uhm, Jae Sun; Seo, Suk Min et al.
In: Biochemical and Biophysical Research Communications, Vol. 402, No. 4, 26.11.2010, p. 577-582.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

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AU - Jung, Hae Ok

AU - Uhm, Jae Sun

AU - Seo, Suk Min

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AU - Youn, Ho Joong

AU - Baek, Sang Hong

AU - Chung, Wook Sung

AU - Seung, Ki Bae

N1 - Funding Information: This research was supported by Seoul St. Mary’s Clinical Medicine Research Program year of 2009 through the Catholic University of Korea. Anti-LRP1 IgG, human recombinant receptor-associated protein (RAP), minireceptor of LRP1 mLRP4, and MMP2 and MMP9 promoter luciferase vectors were kindly provided by Dr. Heesang Song.

PY - 2010/11/26

Y1 - 2010/11/26

N2 - Angiotensin II (Ang II), one of the main vasoactive hormones of the renin-angiotensin system, contributes to the development and progression of atherosclerosis by inducing vascular smooth muscle cells (VSMCs) migration. Although previous studies have shown that Ang II upregulates low density lipoprotein receptor-related protein 1 (LRP1) expression in VSMCs and increases VSMCs migration, the role of LRP1 in Ang II-induced VSMCs migration remains unclear. Here, we reveal a novel mechanism by which LRP1 induces the expression of matrix metalloproteinase 2 (MMP2) and thereby promotes the migration of rat aortic SMCs (RAoSMCs). Knockdown of LRP1 expression greatly decreased RAoSMCs migration, which was rescued by forced expression of a functional LRP1 minireceptor, suggesting that LRP1 is a key regulator of Ang II-induced RAoSMCs migration. Inhibition of ligand binding to LRP1 by the specific antagonist receptor-associated protein (RAP) also led to reduced RAoSMCs migration. Because MMPs play critical roles in RAoSMCs migration, we examined the expression of several MMPs and found that the expression of functional MMP2 was selectively increased by Ang II treatment and decreased in LRP1-knockdown RAoSMCs. More interestingly, reduced MMP2 expression in LRP1-knockdown cells was completely rescued by exogenous expression of mLRP4, suggesting that MMP2 is a downstream regulator of LRP1 in Ang II-induced RAoSMCs migration. Together, our data strongly suggest that LRP1 promotes the migration of RAoSMCs by regulating the expression and function of MMP2.

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Angiotensin II-induced smooth muscle cell migration is mediated by LDL receptor-related protein 1 via regulation of matrix metalloproteinase 2 expression

Abstract

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Keywords

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