miR-320a affects spinal cord edema through negatively regulating aquaporin-1 of blood–spinal cord barrier during bimodal stage after ischemia reperfusion injury in rats
Authors: Hong Ma
Zhi-Lin Wang
Wen-Fei Tan
Xi-Jia Sun
Bo Fang
Xiao-Qian Li
Zai-Li Zhang
Journal: BMC Neuroscience (2016)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Spinal cord edema; ischemia reperfusion injury; blood-spinal cord barrier; Aquaporin 1; microRNAs
Affiliations: Department of Anesthesiology, First Affiliated Hospital, China Medical University, Shenyang, 110001, Liaoning, China. .

Abstract:  Background: Spinal cord edema is a serious complication and pathophysiological change after ischemia reperfusion (IR) injury. It has been demonstrated closely associated with bimodal disruption of blood-spinal cord barrier (BSCB) in our previous work. Aquaporin (AQP)1 plays important but contradictory roles in water homeostasis. Recently, microRNAs (miRs) effectively regulate numerous target mRNAs during ischemia. However, whether miRs are able to protect against dimodal disruption of BSCB by regulating perivascular AQP1 remains to be elucidated. Results: Spinal water content and EB extravasation were suggested as a bimodal distribution in directly proportion to AQP1, since all maximal changes were detected at 12 and 48 h after reperfusion. Further TEM and double immunofluorescence showed that former disruption of BSCB at 12 h was attributed to cytotoxic edema by up-regulated AQP1 expressions in astrocytes, whereas the latter at 48 h was mixed with vasogenic edema with both endothelial cells and astrocytes involvement. Microarray analysis revealed that at 12 h post-injury, ten miRs were upregulated (&gt;2.0 fold) and seven miRs were downregulated (&lt;0.5 fold) and at 48 h, ten miRs were upregulated and eleven were downregulated compared to Sham-operated controls. Genomic screening and luciferase assays identified that miR-320a was a potential modulator of AQP1 in spinal cord after IR in vitro. In vivo, compared to rats in IR and negative control group, intrathecal infusion of miR-320a mimic attenuated IR-induced lower limb motor function deficits and BSCB dysfunction as decreased EB extravasation and spinal water content through down-regulating AQP1 expressions, whereas pretreated with miR-320a AMO reversed above effects. Conclusion: These findings indicate miR-320a directly and functionally affects spinal cord edema through negatively regulating AQP1 of BSCB after IR. 

Retracted: Yes

PubPeer comments:
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 #1 We thank you for your comments. We have sent all original data, along with your comments, to the editors of JEM and Diabetes. , 
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 Figure 2H. More similar than expected. UCP1 and UCP3 panels do not look like they come from the same blot. ![file] , 
 Thank you for binging up the question, because the molecular weight of UCP1 (MW33kd) and UCP3 (MW 34kd) are very close, 2 gels were run in parallel with the same samples. Here are the original WB blots: , 
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 #10  2 gels were run in parallel with the same samples . There is only 1 actin blot. , 
 2021 retraction. https: diabetes.diabetesjournals.org content diabetes early 2021 06 17 db21-rt08c.full.pdf Statement of Retraction Statement of Retraction. Qilong Wang, Zhonglin Xie, Wencheng Zhang, Jun Zhou, Yue Wu, Miao Zhang, Huaiping Zhu, and Ming-Hui Zou. Myeloperoxidase Deletion Prevents High-Fat Dietu2013Induced Obesity and Insulin Resistance. Diabetes 2014;63:4172u20134185. DOI: 10.2337 db14-0026. PMID: 25024373. PMCID: PMC4238009 American Diabetes Association https: doi.org 10.2337 db21-rt08c At the request of the University of Oklahoma Health Sciences Center (OUHSC), the above-cited article has been retracted. An OUHSC investigation into the integrity of the data presented in the article concluded that multiple Western blot figures were falu0002sified. The falsifications are described below. u2022 Lanes 2 and 4 of the Fig. 7G P-Akt (S473) Western blot are duplicate bands shown with different treatment labels. u2022 Lanes 3, 6, and 7 of the Fig. 7H P85 Western blot are duplicate bands shown with different treatment labels. u2022 The Fig. 7H IRS-1 Western blot is reused and shown with different treatment labels in lanes 1u20137 of Fig. 4B IRS1 in the following publication: Zhou J, Wang Q, Ding Y, Zou M-H. Hypochlorous acid via peroxynitrite activates protein kinase Cu and insulin resistance in adipocytes. J Mol Endocrinol 2015;54:25u201337. DOI: 10.1530 JME-14-0213. PMID: 25381390. PMCID: PMC4261204 u2022 The first four lanes of Fig. 7H IRS-1 are also reused in lanes 1u20134 of Fig. 2A IRS1 in the above-cited publication. u2022 Lanes 1 and 4 of Fig. 7G P-IRb are duplicates. u2022 Lanes 1, 3, 5, and 7 of Fig. 7I 3-NT are duplicates. The American Diabetes Associationu2019s (ADAu2019s) Panel on Ethical Scientific Programs conu0002curs with the OUHSC investigative report and has reviewed and approved this stateu0002ment of retraction. More information about ADAu2019s retraction policies and procedures can be found at https: diabetesjournals.org content journal-policies ,