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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| Format: | Article |
| Language: | English |
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Nature Portfolio
2017-07-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-05868-y |
| _version_ | 1827310206358388736 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-24T19:55:57Z |
| format | Article |
| id | doaj.art-5d8c17ad9ff94ce4a6d3f806f84018eb |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T19:55:57Z |
| publishDate | 2017-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5d8c17ad9ff94ce4a6d3f806f84018eb2024-03-24T12:21:31ZengNature PortfolioScientific Reports2045-23222017-07-017111310.1038/s41598-017-05868-yThe adipokine leptin modulates adventitial pericyte functions by autocrine and paracrine signallingFederica Riu0Sadie C. Slater1Eva Jover Garcia2Iker Rodriguez-Arabaolaza3Valeria Alvino4Elisa Avolio5Giuseppe Mangialardi6Andrea Cordaro7Simon Satchell8Carlo Zebele9Andrea Caporali10Gianni Angelini11Paolo Madeddu12Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryCentre for Cardiovascular Science, Queen’s Medical Research InstituteBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryBristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol Royal InfirmaryAbstract 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.https://doi.org/10.1038/s41598-017-05868-y |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-017-05868-y |
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