Cargando…
Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps
Surgical flaps are frequently affected by ischemia/reperfusion (I/R) injury. Calcium-sensing receptor (CaSR) and stromal cell-derived factor-1α (SDF-1α) are closely associated with myocardial I/R injury. This study was performed to evaluate the feasibility of applying SDF-1α to counteract CaSR activ...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820583/ https://www.ncbi.nlm.nih.gov/pubmed/29568770 http://dx.doi.org/10.1155/2018/8945850 |
_version_ | 1783301400890966016 |
---|---|
author | Song, Li Gao, Li-Na Wang, Jun Thapa, Swosti Li, Yong Zhong, Xiao-Bo Zhao, Hong-Wei Xiang, Xue-Rong Zhang, Fu-Gui Ji, Ping |
author_facet | Song, Li Gao, Li-Na Wang, Jun Thapa, Swosti Li, Yong Zhong, Xiao-Bo Zhao, Hong-Wei Xiang, Xue-Rong Zhang, Fu-Gui Ji, Ping |
author_sort | Song, Li |
collection | PubMed |
description | Surgical flaps are frequently affected by ischemia/reperfusion (I/R) injury. Calcium-sensing receptor (CaSR) and stromal cell-derived factor-1α (SDF-1α) are closely associated with myocardial I/R injury. This study was performed to evaluate the feasibility of applying SDF-1α to counteract CaSR activation-mediated I/R injury in ischemic free flaps. Free flaps that underwent ischemia for 3 h were equally randomized into five groups: CaCl(2), NPS2143 + CaCl(2), SDF-1α + CaCl(2), AMD3100 + SDF-1α + CaCl(2), and normal saline. The free flaps were harvested to evaluate flap necrosis and neovascularization after 2 h or 7 d of reperfusion. p-CaSR/CaSR was extensively expressed in vascular endothelial cells of free flaps after I/R injury, and activation of the SDF-1α/CXCR4 axis and NPS2143 could reduce the expression of cleaved caspase-3, caspase-9, FAS, Cyt-c, and Bax and increase Bcl-2 expression; the opposite was true after CaSR activation. Interestingly, initiation of the SDF-1α/CXCR4 axis might abrogate CaSR activation-induced I/R injury through enhancement of microvessel density. In conclusion, CaSR might become a novel therapeutic target of free flaps affected by I/R injury. Activation of the SDF-1α/CXCR4 axis and NPS2143 could counteract CaSR activation-mediated I/R injury and promote free flap survival through inhibition of caspase-3/caspase-9-related cell apoptosis and enhancement of neovascularization. |
format | Online Article Text |
id | pubmed-5820583 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-58205832018-03-22 Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps Song, Li Gao, Li-Na Wang, Jun Thapa, Swosti Li, Yong Zhong, Xiao-Bo Zhao, Hong-Wei Xiang, Xue-Rong Zhang, Fu-Gui Ji, Ping Biomed Res Int Research Article Surgical flaps are frequently affected by ischemia/reperfusion (I/R) injury. Calcium-sensing receptor (CaSR) and stromal cell-derived factor-1α (SDF-1α) are closely associated with myocardial I/R injury. This study was performed to evaluate the feasibility of applying SDF-1α to counteract CaSR activation-mediated I/R injury in ischemic free flaps. Free flaps that underwent ischemia for 3 h were equally randomized into five groups: CaCl(2), NPS2143 + CaCl(2), SDF-1α + CaCl(2), AMD3100 + SDF-1α + CaCl(2), and normal saline. The free flaps were harvested to evaluate flap necrosis and neovascularization after 2 h or 7 d of reperfusion. p-CaSR/CaSR was extensively expressed in vascular endothelial cells of free flaps after I/R injury, and activation of the SDF-1α/CXCR4 axis and NPS2143 could reduce the expression of cleaved caspase-3, caspase-9, FAS, Cyt-c, and Bax and increase Bcl-2 expression; the opposite was true after CaSR activation. Interestingly, initiation of the SDF-1α/CXCR4 axis might abrogate CaSR activation-induced I/R injury through enhancement of microvessel density. In conclusion, CaSR might become a novel therapeutic target of free flaps affected by I/R injury. Activation of the SDF-1α/CXCR4 axis and NPS2143 could counteract CaSR activation-mediated I/R injury and promote free flap survival through inhibition of caspase-3/caspase-9-related cell apoptosis and enhancement of neovascularization. Hindawi 2018-01-11 /pmc/articles/PMC5820583/ /pubmed/29568770 http://dx.doi.org/10.1155/2018/8945850 Text en Copyright © 2018 Li Song et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Song, Li Gao, Li-Na Wang, Jun Thapa, Swosti Li, Yong Zhong, Xiao-Bo Zhao, Hong-Wei Xiang, Xue-Rong Zhang, Fu-Gui Ji, Ping Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps |
title | Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps |
title_full | Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps |
title_fullStr | Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps |
title_full_unstemmed | Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps |
title_short | Stromal Cell-Derived Factor-1α Alleviates Calcium-Sensing Receptor Activation-Mediated Ischemia/Reperfusion Injury by Inhibiting Caspase-3/Caspase-9-Induced Cell Apoptosis in Rat Free Flaps |
title_sort | stromal cell-derived factor-1α alleviates calcium-sensing receptor activation-mediated ischemia/reperfusion injury by inhibiting caspase-3/caspase-9-induced cell apoptosis in rat free flaps |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5820583/ https://www.ncbi.nlm.nih.gov/pubmed/29568770 http://dx.doi.org/10.1155/2018/8945850 |
work_keys_str_mv | AT songli stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT gaolina stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT wangjun stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT thapaswosti stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT liyong stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT zhongxiaobo stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT zhaohongwei stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT xiangxuerong stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT zhangfugui stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps AT jiping stromalcellderivedfactor1aalleviatescalciumsensingreceptoractivationmediatedischemiareperfusioninjurybyinhibitingcaspase3caspase9inducedcellapoptosisinratfreeflaps |