Background:The protective effect of mesenchymal stem cells(MSCs)on cardiac ischemia-reperfusion(I/R)injury has been widely reported.Dental pulp-derived mesenchymal stem cells(DP-MSCs)have therapeutic effects on variou...Background:The protective effect of mesenchymal stem cells(MSCs)on cardiac ischemia-reperfusion(I/R)injury has been widely reported.Dental pulp-derived mesenchymal stem cells(DP-MSCs)have therapeutic effects on various diseases,including diabetes and cirrhosis.This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism.Methods:Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic.The infarct volume,fibrotic area,pyroptosis,inflammation level,and cardiac function were measured.Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic,miR-19a-3p inhibitor,or negative control.Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase(IRF-8/MAPK)pathway were measured.Results:DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis.The upregulation of miR-19a-3p protected cardiac function,inhibited cardiomyocyte pyroptosis,and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice.DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R.Conclusion:DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.展开更多
基金supported by grants from the National High Level Hospital Clinical Research Funding(No.BJ-2022-117)the special project on basic and applied research of clinical medicine of Shanghai Wu Mengchao Medical Science and Technology Foundation(No.JJHXM-2019018)+1 种基金Beijing Hospital Research Project(No.BJ-2019-147)Beijing Jiekai Cardiovascular Health Foundation(No.2022-062).
文摘Background:The protective effect of mesenchymal stem cells(MSCs)on cardiac ischemia-reperfusion(I/R)injury has been widely reported.Dental pulp-derived mesenchymal stem cells(DP-MSCs)have therapeutic effects on various diseases,including diabetes and cirrhosis.This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism.Methods:Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic.The infarct volume,fibrotic area,pyroptosis,inflammation level,and cardiac function were measured.Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic,miR-19a-3p inhibitor,or negative control.Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase(IRF-8/MAPK)pathway were measured.Results:DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis.The upregulation of miR-19a-3p protected cardiac function,inhibited cardiomyocyte pyroptosis,and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice.DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R.Conclusion:DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.