Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.

<h4>Background</h4>Sortilin, a member of the Vps10p-domain receptor family, has been demonstrated a key regulator in mediating cellular response to pro-neurotrophins. In the present study, we investigated the role of sortilin in the apoptotic pathway of vascular smooth muscle cells.<h...

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Autores principales:	Luisa Campagnolo, Gaetana Costanza, Arianna Francesconi, Gaetano Arcuri, Ilana Moscatelli, Augusto Orlandi
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/dd3703b608574afd9b290ba3780569c2
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spelling	oai:doaj.org-article:dd3703b608574afd9b290ba3780569c22021-11-18T08:38:54ZSortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.1932-620310.1371/journal.pone.0084969https://doaj.org/article/dd3703b608574afd9b290ba3780569c22014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24404198/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Sortilin, a member of the Vps10p-domain receptor family, has been demonstrated a key regulator in mediating cellular response to pro-neurotrophins. In the present study, we investigated the role of sortilin in the apoptotic pathway of vascular smooth muscle cells.<h4>Methods and principal findings</h4>Immunohistochemistry revealed that sortilin was barely detectable in human and rat normal young vessels, while its expression was increased in human fibroatheromatous plaques. Sortilin immunodetection was also marked in the neointima of the rat aorta fifteen days after ballooning.In vitro, rat aortic intimal cells expressed higher sortilin levels than normal media SMCs; sortilin was distributed in the cytoplasm and in correspondence of the cell membrane. After 48 h, pro-nerve growth factor (proNGF) induced the strong dose-dependent increase of intimal cell apoptosis and the accumulation of sortilin protein. ProNGF was a more potent apoptotic inducer than equimolar or even higher concentration of NGF, whereas brain derived neutrotrophic factor was ineffective. Targeted interfering RNA-mediated sortilin reduction counteracted proNGF-induced apoptosis without affecting p75(NTR) expression. ProNGF-induced apoptosis was associated to NF-κB down-regulation and bax increase. Inhibition of NF-κB activity increased intimal cell apoptosis that did not further increase with the addition of proNGF.<h4>Conclusions</h4>Our results indicate that sortilin expression characterizes human atheromatous lesions and rat aortic post-injury neointima, and suggest that sortilin represents an important regulator of proNGF-induced SMC apoptosis and arterial remodeling.Luisa CampagnoloGaetana CostanzaArianna FrancesconiGaetano ArcuriIlana MoscatelliAugusto OrlandiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e84969 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luisa Campagnolo Gaetana Costanza Arianna Francesconi Gaetano Arcuri Ilana Moscatelli Augusto Orlandi Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.
description	<h4>Background</h4>Sortilin, a member of the Vps10p-domain receptor family, has been demonstrated a key regulator in mediating cellular response to pro-neurotrophins. In the present study, we investigated the role of sortilin in the apoptotic pathway of vascular smooth muscle cells.<h4>Methods and principal findings</h4>Immunohistochemistry revealed that sortilin was barely detectable in human and rat normal young vessels, while its expression was increased in human fibroatheromatous plaques. Sortilin immunodetection was also marked in the neointima of the rat aorta fifteen days after ballooning.In vitro, rat aortic intimal cells expressed higher sortilin levels than normal media SMCs; sortilin was distributed in the cytoplasm and in correspondence of the cell membrane. After 48 h, pro-nerve growth factor (proNGF) induced the strong dose-dependent increase of intimal cell apoptosis and the accumulation of sortilin protein. ProNGF was a more potent apoptotic inducer than equimolar or even higher concentration of NGF, whereas brain derived neutrotrophic factor was ineffective. Targeted interfering RNA-mediated sortilin reduction counteracted proNGF-induced apoptosis without affecting p75(NTR) expression. ProNGF-induced apoptosis was associated to NF-κB down-regulation and bax increase. Inhibition of NF-κB activity increased intimal cell apoptosis that did not further increase with the addition of proNGF.<h4>Conclusions</h4>Our results indicate that sortilin expression characterizes human atheromatous lesions and rat aortic post-injury neointima, and suggest that sortilin represents an important regulator of proNGF-induced SMC apoptosis and arterial remodeling.
format	article
author	Luisa Campagnolo Gaetana Costanza Arianna Francesconi Gaetano Arcuri Ilana Moscatelli Augusto Orlandi
author_facet	Luisa Campagnolo Gaetana Costanza Arianna Francesconi Gaetano Arcuri Ilana Moscatelli Augusto Orlandi
author_sort	Luisa Campagnolo
title	Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.
title_short	Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.
title_full	Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.
title_fullStr	Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.
title_full_unstemmed	Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.
title_sort	sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/dd3703b608574afd9b290ba3780569c2
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Sortilin expression is essential for pro-nerve growth factor-induced apoptosis of rat vascular smooth muscle cells.

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