Chemotactic effect of prorenin on human aortic smooth muscle cells: A novel function of the (pro)renin receptor

Carolina M. Greco, Marina Camera, Laura Facchinetti, Marta Brambilla, Sara Pellegrino, Maria Luisa Gelmi, Elena Tremoli, Alberto Corsini, Nicola Ferri

Research output: Contribution to journalArticle

Abstract

Aims: The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. Methods and results: PRR was expressed in human mammary arteries and in cultured human aortic SMCs. Prorenin induced SMC migration in a dose-dependent manner, as assessed by Boyden chamber chemotaxis assay, and increased SMC random motility, as determined by video microscopy. The prorenin decoy peptide inhibited SMC migration in response to prorenin, and knockdown of PRR by small interfering RNA completely inhibited the migratory response to prorenin, demonstrating that the chemotactic action of prorenin is mediated by the PRR. Prorenin induced cytoskeleton reorganization and lamellipodia formation and increased the intracellular levels of both RhoA-GTP and Rac1-GTP through PRR. These effects were required for SMC migration, because the suppression by small interfering RNA of either Rac1 or RhoA GTP-bound forms completely blocked the PRR-mediated chemotactic effect. Prorenin also induced the formation of larger focal adhesions and cleavage of the focal adhesion kinase (pp125 FAK) into two main fragments with molecular weights of 50 and 90 kDa. The generation of these two fragments of pp125FAK was reduced by the calpain inhibitor ALLN, which also inhibited SMC migration in response to prorenin. Conclusions: These results demonstrate that prorenin is a chemotactic factor for human aortic SMCs expressing PRR. This effect is elicited through reorganization of the cytoskeleton and focal adhesion, activation of RhoA and Rac1, and calpain-mediated cleavage of pp125FAK.

Original languageEnglish
Pages (from-to)366-374
Number of pages9
JournalCardiovascular Research
Volume95
Issue number3
DOIs
Publication statusPublished - 2012

Fingerprint

Renin
Smooth Muscle Myocytes
Cell Movement
Guanosine Triphosphate
Focal Adhesions
Cytoskeleton
Small Interfering RNA
Video Microscopy
Angiotensin I
Focal Adhesion Protein-Tyrosine Kinases
Pseudopodia
Calpain
Mammary Arteries
prorenin receptor
Chemotactic Factors
Chemotaxis
Molecular Weight
Peptides

Keywords

  • Cell migration
  • Focal adhesion kinase
  • Rac1
  • RhoA
  • Smooth muscle cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Chemotactic effect of prorenin on human aortic smooth muscle cells : A novel function of the (pro)renin receptor. / Greco, Carolina M.; Camera, Marina; Facchinetti, Laura; Brambilla, Marta; Pellegrino, Sara; Gelmi, Maria Luisa; Tremoli, Elena; Corsini, Alberto; Ferri, Nicola.

In: Cardiovascular Research, Vol. 95, No. 3, 2012, p. 366-374.

Research output: Contribution to journalArticle

Greco, Carolina M. ; Camera, Marina ; Facchinetti, Laura ; Brambilla, Marta ; Pellegrino, Sara ; Gelmi, Maria Luisa ; Tremoli, Elena ; Corsini, Alberto ; Ferri, Nicola. / Chemotactic effect of prorenin on human aortic smooth muscle cells : A novel function of the (pro)renin receptor. In: Cardiovascular Research. 2012 ; Vol. 95, No. 3. pp. 366-374.
@article{ae81b2d1fe9f494ab3bf11b6bac6cb98,
title = "Chemotactic effect of prorenin on human aortic smooth muscle cells: A novel function of the (pro)renin receptor",
abstract = "Aims: The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. Methods and results: PRR was expressed in human mammary arteries and in cultured human aortic SMCs. Prorenin induced SMC migration in a dose-dependent manner, as assessed by Boyden chamber chemotaxis assay, and increased SMC random motility, as determined by video microscopy. The prorenin decoy peptide inhibited SMC migration in response to prorenin, and knockdown of PRR by small interfering RNA completely inhibited the migratory response to prorenin, demonstrating that the chemotactic action of prorenin is mediated by the PRR. Prorenin induced cytoskeleton reorganization and lamellipodia formation and increased the intracellular levels of both RhoA-GTP and Rac1-GTP through PRR. These effects were required for SMC migration, because the suppression by small interfering RNA of either Rac1 or RhoA GTP-bound forms completely blocked the PRR-mediated chemotactic effect. Prorenin also induced the formation of larger focal adhesions and cleavage of the focal adhesion kinase (pp125 FAK) into two main fragments with molecular weights of 50 and 90 kDa. The generation of these two fragments of pp125FAK was reduced by the calpain inhibitor ALLN, which also inhibited SMC migration in response to prorenin. Conclusions: These results demonstrate that prorenin is a chemotactic factor for human aortic SMCs expressing PRR. This effect is elicited through reorganization of the cytoskeleton and focal adhesion, activation of RhoA and Rac1, and calpain-mediated cleavage of pp125FAK.",
keywords = "Cell migration, Focal adhesion kinase, Rac1, RhoA, Smooth muscle cells",
author = "Greco, {Carolina M.} and Marina Camera and Laura Facchinetti and Marta Brambilla and Sara Pellegrino and Gelmi, {Maria Luisa} and Elena Tremoli and Alberto Corsini and Nicola Ferri",
year = "2012",
doi = "10.1093/cvr/cvs204",
language = "English",
volume = "95",
pages = "366--374",
journal = "Cardiovascular Research",
issn = "0008-6363",
publisher = "Oxford University Press",
number = "3",

}

TY - JOUR

T1 - Chemotactic effect of prorenin on human aortic smooth muscle cells

T2 - A novel function of the (pro)renin receptor

AU - Greco, Carolina M.

AU - Camera, Marina

AU - Facchinetti, Laura

AU - Brambilla, Marta

AU - Pellegrino, Sara

AU - Gelmi, Maria Luisa

AU - Tremoli, Elena

AU - Corsini, Alberto

AU - Ferri, Nicola

PY - 2012

Y1 - 2012

N2 - Aims: The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. Methods and results: PRR was expressed in human mammary arteries and in cultured human aortic SMCs. Prorenin induced SMC migration in a dose-dependent manner, as assessed by Boyden chamber chemotaxis assay, and increased SMC random motility, as determined by video microscopy. The prorenin decoy peptide inhibited SMC migration in response to prorenin, and knockdown of PRR by small interfering RNA completely inhibited the migratory response to prorenin, demonstrating that the chemotactic action of prorenin is mediated by the PRR. Prorenin induced cytoskeleton reorganization and lamellipodia formation and increased the intracellular levels of both RhoA-GTP and Rac1-GTP through PRR. These effects were required for SMC migration, because the suppression by small interfering RNA of either Rac1 or RhoA GTP-bound forms completely blocked the PRR-mediated chemotactic effect. Prorenin also induced the formation of larger focal adhesions and cleavage of the focal adhesion kinase (pp125 FAK) into two main fragments with molecular weights of 50 and 90 kDa. The generation of these two fragments of pp125FAK was reduced by the calpain inhibitor ALLN, which also inhibited SMC migration in response to prorenin. Conclusions: These results demonstrate that prorenin is a chemotactic factor for human aortic SMCs expressing PRR. This effect is elicited through reorganization of the cytoskeleton and focal adhesion, activation of RhoA and Rac1, and calpain-mediated cleavage of pp125FAK.

AB - Aims: The discovery of a specific prorenin receptor (PRR) suggests a biological function of prorenin that is independent of angiotensin I production. In the present study, we investigated the role of PRR on smooth muscle cell (SMC) migration. Methods and results: PRR was expressed in human mammary arteries and in cultured human aortic SMCs. Prorenin induced SMC migration in a dose-dependent manner, as assessed by Boyden chamber chemotaxis assay, and increased SMC random motility, as determined by video microscopy. The prorenin decoy peptide inhibited SMC migration in response to prorenin, and knockdown of PRR by small interfering RNA completely inhibited the migratory response to prorenin, demonstrating that the chemotactic action of prorenin is mediated by the PRR. Prorenin induced cytoskeleton reorganization and lamellipodia formation and increased the intracellular levels of both RhoA-GTP and Rac1-GTP through PRR. These effects were required for SMC migration, because the suppression by small interfering RNA of either Rac1 or RhoA GTP-bound forms completely blocked the PRR-mediated chemotactic effect. Prorenin also induced the formation of larger focal adhesions and cleavage of the focal adhesion kinase (pp125 FAK) into two main fragments with molecular weights of 50 and 90 kDa. The generation of these two fragments of pp125FAK was reduced by the calpain inhibitor ALLN, which also inhibited SMC migration in response to prorenin. Conclusions: These results demonstrate that prorenin is a chemotactic factor for human aortic SMCs expressing PRR. This effect is elicited through reorganization of the cytoskeleton and focal adhesion, activation of RhoA and Rac1, and calpain-mediated cleavage of pp125FAK.

KW - Cell migration

KW - Focal adhesion kinase

KW - Rac1

KW - RhoA

KW - Smooth muscle cells

UR - http://www.scopus.com/inward/record.url?scp=84871707900&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84871707900&partnerID=8YFLogxK

U2 - 10.1093/cvr/cvs204

DO - 10.1093/cvr/cvs204

M3 - Article

C2 - 22721990

AN - SCOPUS:84871707900

VL - 95

SP - 366

EP - 374

JO - Cardiovascular Research

JF - Cardiovascular Research

SN - 0008-6363

IS - 3

ER -