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Leptin Induces Sca-1(+) Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models
OBJECTIVE—: Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1(+) vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1(+) pr...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671780/ https://www.ncbi.nlm.nih.gov/pubmed/28935755 http://dx.doi.org/10.1161/ATVBAHA.117.309852 |
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author | Xie, Yao Potter, Claire M.F. Le Bras, Alexandra Nowak, Witold N. Gu, Wenduo Bhaloo, Shirin Issa Zhang, Zhongyi Hu, Yanhua Zhang, Li Xu, Qingbo |
author_facet | Xie, Yao Potter, Claire M.F. Le Bras, Alexandra Nowak, Witold N. Gu, Wenduo Bhaloo, Shirin Issa Zhang, Zhongyi Hu, Yanhua Zhang, Li Xu, Qingbo |
author_sort | Xie, Yao |
collection | PubMed |
description | OBJECTIVE—: Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1(+) vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1(+) progenitor cells migration and neointimal formation and to understand the underlying mechanisms. APPROACH AND RESULTS—: Sca-1(+) progenitor cells from the vessel wall of Lepr(+/+) and Lepr(−/−) mice were cultured and purified. The migration of Lepr(+/+) Sca-1(+) progenitor cells in vitro was markedly induced by leptin. Western blotting and kinase assays revealed that leptin induced the activation of phosphorylated signal transducer and activator of transcription 3, phosphorylated extracellular signal–regulated kinases 1/2, pFAK (phosphorylated focal adhesion kinase), and Rac1 (ras-related C3 botulinum toxin substrate 1)/Cdc42 (cell division control protein 42 homolog). In a mouse femoral artery guidewire injury model, an increased expression of leptin in both injured vessels and serum was observed 24 hours post-surgery. RFP (red fluorescent protein)-Sca-1(+) progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery. RFP(+) cells were observed in the intima 24 hours post-surgery, subsequently increasing neointimal lesions at 2 weeks when compared with the arteries without seeded cells. This increase was reduced by pre-treatment of Sca-1(+) cells with a leptin antagonist. Guidewire injury could only induce minor neointima in Lepr(−/−) mice 2 weeks post-surgery. However, transplantation of Lepr(+/+) Sca-1(+) progenitor cells into the adventitial side of injured artery in Lepr(−/−) mice significantly enhanced neointimal formation. CONCLUSIONS—: Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1(+) progenitor cells via leptin receptor–dependent signal transducer and activator of transcription 3- Rac1/Cdc42-ERK (extracellular signal–regulated kinase)-FAK pathways, which enhanced neointimal formation. |
format | Online Article Text |
id | pubmed-5671780 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-56717802017-11-22 Leptin Induces Sca-1(+) Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models Xie, Yao Potter, Claire M.F. Le Bras, Alexandra Nowak, Witold N. Gu, Wenduo Bhaloo, Shirin Issa Zhang, Zhongyi Hu, Yanhua Zhang, Li Xu, Qingbo Arterioscler Thromb Vasc Biol Basic Sciences OBJECTIVE—: Leptin is an adipokine initially thought to be a metabolic factor. Recent publications have shown its roles in inflammation and vascular disease, to which Sca-1(+) vascular progenitor cells within the vessel wall may contribute. We sought to elucidate the effects of leptin on Sca-1(+) progenitor cells migration and neointimal formation and to understand the underlying mechanisms. APPROACH AND RESULTS—: Sca-1(+) progenitor cells from the vessel wall of Lepr(+/+) and Lepr(−/−) mice were cultured and purified. The migration of Lepr(+/+) Sca-1(+) progenitor cells in vitro was markedly induced by leptin. Western blotting and kinase assays revealed that leptin induced the activation of phosphorylated signal transducer and activator of transcription 3, phosphorylated extracellular signal–regulated kinases 1/2, pFAK (phosphorylated focal adhesion kinase), and Rac1 (ras-related C3 botulinum toxin substrate 1)/Cdc42 (cell division control protein 42 homolog). In a mouse femoral artery guidewire injury model, an increased expression of leptin in both injured vessels and serum was observed 24 hours post-surgery. RFP (red fluorescent protein)-Sca-1(+) progenitor cells in Matrigel were applied to the adventitia of the injured femoral artery. RFP(+) cells were observed in the intima 24 hours post-surgery, subsequently increasing neointimal lesions at 2 weeks when compared with the arteries without seeded cells. This increase was reduced by pre-treatment of Sca-1(+) cells with a leptin antagonist. Guidewire injury could only induce minor neointima in Lepr(−/−) mice 2 weeks post-surgery. However, transplantation of Lepr(+/+) Sca-1(+) progenitor cells into the adventitial side of injured artery in Lepr(−/−) mice significantly enhanced neointimal formation. CONCLUSIONS—: Upregulation of leptin levels in both the vessel wall and the circulation after vessel injury promoted the migration of Sca-1(+) progenitor cells via leptin receptor–dependent signal transducer and activator of transcription 3- Rac1/Cdc42-ERK (extracellular signal–regulated kinase)-FAK pathways, which enhanced neointimal formation. Lippincott Williams & Wilkins 2017-11 2017-10-25 /pmc/articles/PMC5671780/ /pubmed/28935755 http://dx.doi.org/10.1161/ATVBAHA.117.309852 Text en © 2017 The Authors. Arteriosclerosis, Thrombosis, and Vascular Biology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial (http://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Basic Sciences Xie, Yao Potter, Claire M.F. Le Bras, Alexandra Nowak, Witold N. Gu, Wenduo Bhaloo, Shirin Issa Zhang, Zhongyi Hu, Yanhua Zhang, Li Xu, Qingbo Leptin Induces Sca-1(+) Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models |
title | Leptin Induces Sca-1(+) Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models |
title_full | Leptin Induces Sca-1(+) Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models |
title_fullStr | Leptin Induces Sca-1(+) Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models |
title_full_unstemmed | Leptin Induces Sca-1(+) Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models |
title_short | Leptin Induces Sca-1(+) Progenitor Cell Migration Enhancing Neointimal Lesions in Vessel-Injury Mouse Models |
title_sort | leptin induces sca-1(+) progenitor cell migration enhancing neointimal lesions in vessel-injury mouse models |
topic | Basic Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671780/ https://www.ncbi.nlm.nih.gov/pubmed/28935755 http://dx.doi.org/10.1161/ATVBAHA.117.309852 |
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