Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)
Min Xu,1,* Dingchao Xiang,2,* Wenhua Wang,1 Long Chen,1 Wei Lu,1 Feng Cheng3 1Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan City, Jiangsu Province, 215300, People’s Republic...
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Dove Medical Press
2021
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oai:doaj.org-article:2cc1d8d7bb2a423a916d5f13d81c8f532021-12-02T19:06:31ZInhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)1178-2021https://doaj.org/article/2cc1d8d7bb2a423a916d5f13d81c8f532021-10-01T00:00:00Zhttps://www.dovepress.com/inhibition-of-mir-448-3p-attenuates-cerebral-ischemic-injury-by-upregu-peer-reviewed-fulltext-article-NDThttps://doaj.org/toc/1178-2021Min Xu,1,* Dingchao Xiang,2,* Wenhua Wang,1 Long Chen,1 Wei Lu,1 Feng Cheng3 1Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan City, Jiangsu Province, 215300, People’s Republic of China; 2Department of Neurosurgery, Wuxi clinical medical school of Anhui Medical University, 904th Hospital of PLA(Taihu Hospital of Wuxi), Wuxi, 214000, People’s Republic of China; 3Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng ChengDepartment of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu Province, People’s Republic of ChinaTel +86-13913208695Email fengchengjiangsu@163.comBackground: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator responsible for oxidative stress in brain injury. This study aimed to investigate the potential mechanism of miR-448-3p and Nrf2 in cerebral ischemia/reperfusion (I/R) injury.Methods: In vitro and in vivo cerebral I/R injury models were constructed, and Nrf2 expression levels were detected by qRT-PCR and Western blot. The potential miRNAs for Nrf2 were predicted by bioinformatic analysis. The binding interaction between miR-448-3p and Nrf2 was determined by luciferase reporter assay. The effects of miR-448-3p on neurological deficit, infarct volume, and brain water content in mice were tested. The effects of miR-448-3p on oxidative stress indicators (SOD activity, MDA content, and ROS production) were detected by commercial assay kits. The levels of HO-1 and cleaved caspase-3 were evaluated by Western blot. Cell viability was evaluated by MTT assay, and cell apoptosis was evaluated by TUNEL staining and flow cytometry.Results: Nrf2 was significantly downregulated and miR-448-3p was upregulated in cerebral I/R injury both in vivo and in vitro. MiR-448-3p downregulation efficiently attenuated brain injury and reduced oxidative stress and apoptosis. MiR-448-3p was identified to act as ceRNA of Nrf2 and negatively regulated Nrf2 expression, which was consistent with the animal studies. In addition, Nrf2 silencing obviously attenuated the neuroprotective effects of miR-448-3p inhibitor in vitro.Conclusion: MiR-448-3p participated in the regulation of cerebral I/R injury via inhibiting Nrf2.Keywords: ischemia/reperfusion, miR-448-3p, Nrf2, oxidative stress, apoptosisXu MXiang DWang WChen LLu WCheng FDove Medical Pressarticleischemia/reperfusionmir-448-3pnrf2oxidative stressapoptosisNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 17, Pp 3147-3158 (2021) |
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DOAJ |
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DOAJ |
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EN |
| topic |
ischemia/reperfusion mir-448-3p nrf2 oxidative stress apoptosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 |
| spellingShingle |
ischemia/reperfusion mir-448-3p nrf2 oxidative stress apoptosis Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Xu M Xiang D Wang W Chen L Lu W Cheng F Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) |
| description |
Min Xu,1,* Dingchao Xiang,2,* Wenhua Wang,1 Long Chen,1 Wei Lu,1 Feng Cheng3 1Department of Neurosurgery, Kunshan Hospital of Traditional Chinese Medicine, Kunshan Affiliated Hospital of Nanjing University of Chinese Medicine, Kunshan City, Jiangsu Province, 215300, People’s Republic of China; 2Department of Neurosurgery, Wuxi clinical medical school of Anhui Medical University, 904th Hospital of PLA(Taihu Hospital of Wuxi), Wuxi, 214000, People’s Republic of China; 3Department of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu Province, People’s Republic of China*These authors contributed equally to this workCorrespondence: Feng ChengDepartment of Neurosurgery, Affiliated Kunshan Hospital of Jiangsu University, Kunshan, 215300, Jiangsu Province, People’s Republic of ChinaTel +86-13913208695Email fengchengjiangsu@163.comBackground: Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator responsible for oxidative stress in brain injury. This study aimed to investigate the potential mechanism of miR-448-3p and Nrf2 in cerebral ischemia/reperfusion (I/R) injury.Methods: In vitro and in vivo cerebral I/R injury models were constructed, and Nrf2 expression levels were detected by qRT-PCR and Western blot. The potential miRNAs for Nrf2 were predicted by bioinformatic analysis. The binding interaction between miR-448-3p and Nrf2 was determined by luciferase reporter assay. The effects of miR-448-3p on neurological deficit, infarct volume, and brain water content in mice were tested. The effects of miR-448-3p on oxidative stress indicators (SOD activity, MDA content, and ROS production) were detected by commercial assay kits. The levels of HO-1 and cleaved caspase-3 were evaluated by Western blot. Cell viability was evaluated by MTT assay, and cell apoptosis was evaluated by TUNEL staining and flow cytometry.Results: Nrf2 was significantly downregulated and miR-448-3p was upregulated in cerebral I/R injury both in vivo and in vitro. MiR-448-3p downregulation efficiently attenuated brain injury and reduced oxidative stress and apoptosis. MiR-448-3p was identified to act as ceRNA of Nrf2 and negatively regulated Nrf2 expression, which was consistent with the animal studies. In addition, Nrf2 silencing obviously attenuated the neuroprotective effects of miR-448-3p inhibitor in vitro.Conclusion: MiR-448-3p participated in the regulation of cerebral I/R injury via inhibiting Nrf2.Keywords: ischemia/reperfusion, miR-448-3p, Nrf2, oxidative stress, apoptosis |
| format |
article |
| author |
Xu M Xiang D Wang W Chen L Lu W Cheng F |
| author_facet |
Xu M Xiang D Wang W Chen L Lu W Cheng F |
| author_sort |
Xu M |
| title |
Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) |
| title_short |
Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) |
| title_full |
Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) |
| title_fullStr |
Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) |
| title_full_unstemmed |
Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) |
| title_sort |
inhibition of mir-448-3p attenuates cerebral ischemic injury by upregulating nuclear factor erythroid 2-related factor 2 (nrf2) |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/2cc1d8d7bb2a423a916d5f13d81c8f53 |
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