The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling

Abstract Transplantation of adventitial pericytes (APCs) improves recovery from tissue ischemia in preclinical animal models by still unknown mechanisms. This study investigates the role of the adipokine leptin (LEP) in the regulation of human APC biological functions. Transcriptomic analysis of APC...

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Autores principales:	Federica Riu, Sadie C. Slater, Eva Jover Garcia, Iker Rodriguez-Arabaolaza, Valeria Alvino, Elisa Avolio, Giuseppe Mangialardi, Andrea Cordaro, Simon Satchell, Carlo Zebele, Andrea Caporali, Gianni Angelini, Paolo Madeddu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d8c17ad9ff94ce4a6d3f806f84018eb
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spelling	oai:doaj.org-article:5d8c17ad9ff94ce4a6d3f806f84018eb2021-12-02T15:06:24ZThe adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling10.1038/s41598-017-05868-y2045-2322https://doaj.org/article/5d8c17ad9ff94ce4a6d3f806f84018eb2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05868-yhttps://doaj.org/toc/2045-2322Abstract Transplantation of adventitial pericytes (APCs) improves recovery from tissue ischemia in preclinical animal models by still unknown mechanisms. This study investigates the role of the adipokine leptin (LEP) in the regulation of human APC biological functions. Transcriptomic analysis of APCs showed components of the LEP signalling pathway are modulated by hypoxia. Kinetic studies indicate cultured APCs release high amounts of immunoreactive LEP following exposure to hypoxia, continuing upon return to normoxia. Secreted LEP activates an autocrine/paracrine loop through binding to the LEP receptor (LEPR) and induction of STAT3 phosphorylation. Titration studies using recombinant LEP and siRNA knockdown of LEP or LEPR demonstrate the adipokine exerts important regulatory roles in APC growth, survival, migration and promotion of endothelial network formation. Heterogeneity in LEP expression and secretion may influence the reparative proficiency of APC therapy. Accordingly, the levels of LEP secretion predict the microvascular outcome of APCs transplantation in a mouse limb ischemia model. Moreover, we found that the expression of the Lepr gene is upregulated on resident vascular cells from murine ischemic muscles, thus providing a permissive milieu to transplanted LEP-expressing APCs. Results highlight a new mechanism responsible for APC adaptation to hypoxia and instrumental to vascular repair.Federica RiuSadie C. SlaterEva Jover GarciaIker Rodriguez-ArabaolazaValeria AlvinoElisa AvolioGiuseppe MangialardiAndrea CordaroSimon SatchellCarlo ZebeleAndrea CaporaliGianni AngeliniPaolo MadedduNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Federica Riu Sadie C. Slater Eva Jover Garcia Iker Rodriguez-Arabaolaza Valeria Alvino Elisa Avolio Giuseppe Mangialardi Andrea Cordaro Simon Satchell Carlo Zebele Andrea Caporali Gianni Angelini Paolo Madeddu The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling
description	Abstract Transplantation of adventitial pericytes (APCs) improves recovery from tissue ischemia in preclinical animal models by still unknown mechanisms. This study investigates the role of the adipokine leptin (LEP) in the regulation of human APC biological functions. Transcriptomic analysis of APCs showed components of the LEP signalling pathway are modulated by hypoxia. Kinetic studies indicate cultured APCs release high amounts of immunoreactive LEP following exposure to hypoxia, continuing upon return to normoxia. Secreted LEP activates an autocrine/paracrine loop through binding to the LEP receptor (LEPR) and induction of STAT3 phosphorylation. Titration studies using recombinant LEP and siRNA knockdown of LEP or LEPR demonstrate the adipokine exerts important regulatory roles in APC growth, survival, migration and promotion of endothelial network formation. Heterogeneity in LEP expression and secretion may influence the reparative proficiency of APC therapy. Accordingly, the levels of LEP secretion predict the microvascular outcome of APCs transplantation in a mouse limb ischemia model. Moreover, we found that the expression of the Lepr gene is upregulated on resident vascular cells from murine ischemic muscles, thus providing a permissive milieu to transplanted LEP-expressing APCs. Results highlight a new mechanism responsible for APC adaptation to hypoxia and instrumental to vascular repair.
format	article
author	Federica Riu Sadie C. Slater Eva Jover Garcia Iker Rodriguez-Arabaolaza Valeria Alvino Elisa Avolio Giuseppe Mangialardi Andrea Cordaro Simon Satchell Carlo Zebele Andrea Caporali Gianni Angelini Paolo Madeddu
author_facet	Federica Riu Sadie C. Slater Eva Jover Garcia Iker Rodriguez-Arabaolaza Valeria Alvino Elisa Avolio Giuseppe Mangialardi Andrea Cordaro Simon Satchell Carlo Zebele Andrea Caporali Gianni Angelini Paolo Madeddu
author_sort	Federica Riu
title	The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling
title_short	The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling
title_full	The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling
title_fullStr	The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling
title_full_unstemmed	The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling
title_sort	adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5d8c17ad9ff94ce4a6d3f806f84018eb
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The adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signalling

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