Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway

Objective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those tr...

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Autores principales:	Tian Chen, Yamei Jiang, Shihao Xu, Yin Celeste Cheuk, Jiyan Wang, Cheng Yang, Ruiming Rong
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	acute kidney injury renal ischemia-reperfusion injury mesenchymal stem cell polyinosinic-polycytidylic acid anti-inflammatory phenotype Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/cf839773cf0345f78f41ddb208f8abdd
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spelling	oai:doaj.org-article:cf839773cf0345f78f41ddb208f8abdd2021-12-01T00:31:21ZPoly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway2296-858X10.3389/fmed.2021.755849https://doaj.org/article/cf839773cf0345f78f41ddb208f8abdd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.755849/fullhttps://doaj.org/toc/2296-858XObjective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those treated with normal saline, untreated mesenchymal stem cells, mesenchymal stem cells treated with lipopolysaccharide (LPS, pro-inflammatory phenotype) and mesenchymal stem cells treated with polyinosinic-polycytidylic acid (poly[I:C], anti-inflammatory phenotype) respectively. The renal function, histopathological damage, circulating inflammation levels and antioxidant capacity of mice were evaluated. The PI3 kinase p85 (PI3K) inhibitor was added into the conventional mesenchymal stem cell cultures in vitro to observe its effects on the secretion of anti-inflammatory cytokines.Results: Mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) could effectively reduce serum creatinine and blood urea nitrogen, attenuate histopathological damage and apoptosis level, decrease the level of circulating pro-inflammatory cytokines and increase the level of circulating anti-inflammatory cytokines, enhance peroxidase activity and reduce malondialdehyde content at each time point. After the addition of the PI3K inhibitor, the mRNA expression and protein secretion of indoleamine 2,3-dioxygenase 1 and heme oxygenase 1 of various mesenchymal stem cells were significantly reduced, and that of mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) was more obvious.Conclusions: Polyriboinosinic-polyribocytidylic acid (poly[I:C]), a synthetic double-stranded RNA, whose pretreatment induces mesenchymal stem cells to differentiate into the anti-inflammatory phenotype. Anti-inflammatory mesenchymal stem cells induced by poly(I:C) can better protect renal function, alleviate tissue damage, reduce circulating inflammation levels and enhance antioxidant capacity, and achieve stronger anti-inflammatory effects through the TLR3/PI3K pathway.Tian ChenTian ChenYamei JiangYamei JiangShihao XuShihao XuYin Celeste CheukYin Celeste CheukJiyan WangCheng YangCheng YangRuiming RongRuiming RongFrontiers Media S.A.articleacute kidney injuryrenal ischemia-reperfusion injurymesenchymal stem cellpolyinosinic-polycytidylic acidanti-inflammatory phenotypeMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	acute kidney injury renal ischemia-reperfusion injury mesenchymal stem cell polyinosinic-polycytidylic acid anti-inflammatory phenotype Medicine (General) R5-920
spellingShingle	acute kidney injury renal ischemia-reperfusion injury mesenchymal stem cell polyinosinic-polycytidylic acid anti-inflammatory phenotype Medicine (General) R5-920 Tian Chen Tian Chen Yamei Jiang Yamei Jiang Shihao Xu Shihao Xu Yin Celeste Cheuk Yin Celeste Cheuk Jiyan Wang Cheng Yang Cheng Yang Ruiming Rong Ruiming Rong Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway
description	Objective: To investigate the effect and protective mechanism of mesenchymal stem cell subpopulations on acute kidney injury by establishing a mouse model of renal ischemia-reperfusion injury.Methods: Male C57BL/6 mice were randomly divided into five groups, namely, sham-operation group and those treated with normal saline, untreated mesenchymal stem cells, mesenchymal stem cells treated with lipopolysaccharide (LPS, pro-inflammatory phenotype) and mesenchymal stem cells treated with polyinosinic-polycytidylic acid (poly[I:C], anti-inflammatory phenotype) respectively. The renal function, histopathological damage, circulating inflammation levels and antioxidant capacity of mice were evaluated. The PI3 kinase p85 (PI3K) inhibitor was added into the conventional mesenchymal stem cell cultures in vitro to observe its effects on the secretion of anti-inflammatory cytokines.Results: Mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) could effectively reduce serum creatinine and blood urea nitrogen, attenuate histopathological damage and apoptosis level, decrease the level of circulating pro-inflammatory cytokines and increase the level of circulating anti-inflammatory cytokines, enhance peroxidase activity and reduce malondialdehyde content at each time point. After the addition of the PI3K inhibitor, the mRNA expression and protein secretion of indoleamine 2,3-dioxygenase 1 and heme oxygenase 1 of various mesenchymal stem cells were significantly reduced, and that of mesenchymal stem cells treated with poly(I:C) (anti-inflammatory phenotype) was more obvious.Conclusions: Polyriboinosinic-polyribocytidylic acid (poly[I:C]), a synthetic double-stranded RNA, whose pretreatment induces mesenchymal stem cells to differentiate into the anti-inflammatory phenotype. Anti-inflammatory mesenchymal stem cells induced by poly(I:C) can better protect renal function, alleviate tissue damage, reduce circulating inflammation levels and enhance antioxidant capacity, and achieve stronger anti-inflammatory effects through the TLR3/PI3K pathway.
format	article
author	Tian Chen Tian Chen Yamei Jiang Yamei Jiang Shihao Xu Shihao Xu Yin Celeste Cheuk Yin Celeste Cheuk Jiyan Wang Cheng Yang Cheng Yang Ruiming Rong Ruiming Rong
author_facet	Tian Chen Tian Chen Yamei Jiang Yamei Jiang Shihao Xu Shihao Xu Yin Celeste Cheuk Yin Celeste Cheuk Jiyan Wang Cheng Yang Cheng Yang Ruiming Rong Ruiming Rong
author_sort	Tian Chen
title	Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway
title_short	Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway
title_full	Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway
title_fullStr	Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway
title_full_unstemmed	Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway
title_sort	poly(i:c)-induced mesenchymal stem cells protect the kidney against ischemia/reperfusion injury via the tlr3/pi3k pathway
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/cf839773cf0345f78f41ddb208f8abdd
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Poly(I:C)-Induced Mesenchymal Stem Cells Protect the Kidney Against Ischemia/Reperfusion Injury via the TLR3/PI3K Pathway

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