HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury PI3K/AKT Pathway
Authors: Xinkui Zhou
Tuanjie Huang
Jiewen Zhang
Fangxia Guan
Qu Xing
Shanshan Ma
Bo Yang
Yaping Wang
Greta Luyuan Yang
Tian Cheng
Tengfei Liu
Ling Xu
Xingxing Zang
Yuanbo Cui
Jiankang Zhou
Journal: Frontiers in Cellular Neuroscience (2018)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: PI3K/AKT; histone deacetylase 1; human umbilical cord derived mesenchymal stem cells; neuroprotection; traumatic brain injury.
Affiliations: School of Life Sciences, Zhengzhou University, Zhengzhou, China., Henan Provincial People's Hospital, Zhengzhou, China., Translational Medicine Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China., The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China., Stuyvesant High School, New York, NY, United States., Department of Microbiology and Immunology, Einstein College of Medicine, Bronx, NY, United States.

Abstract:  Stem cell transplantation is a promising therapy for traumatic brain injury (TBI), but low efficiency of survival and differentiation of transplanted stem cells limits its clinical application. Histone deacetylase 1 (HDAC1) plays important roles in self-renewal of stem cells as well as the recovery of brain disorders. However, little is known about the effects of HDAC1 on the survival and efficacy of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in vivo. In this study, our results showed that HDAC1 silence promoted hUC-MSCs engraftment in the hippocampus and increased the neuroprotective effects of hUC-MSCs in TBI mouse model, which was accompanied by improved neurological function, enhanced neurogenesis, decreased neural apoptosis, and reduced oxidative stress in the hippocampus. Further mechanistic studies revealed that the expressions of phosphorylated PTEN (p-PTEN), phosphorylated Akt (p-Akt), and phosphorylated GSK-3β (p-GSK-3β) were upregulated. Intriguingly, the neuroprotective effects of hUC-MSCs with HDAC1 silence on behavioral performance of TBI mice was markedly attenuated by LY294002, an inhibitor of the PI3K/AKT pathway. Taken together, our findings suggest that hUC-MSCs transplantation with HDAC1 silence may provide a potential strategy for treating TBI in the future. 

Retracted: No

PubPeer comments:
 A Corrigendum on HDAC1 Silence Promotes Neuroprotective Effects of Human Umbilical Cord-Derived Mesenchymal Stem Cells in a Mouse Model of Traumatic Brain Injury via PI3K AKT Pathway by Xu, L., Xing, Q., Huang, T., Zhou, J., Liu, T., Cui, Y., et al. (2019). Front. Cell. Neurosci. 12:498. doi: 10.3389 fncel.2018.00498 In the original article, there was a mistake in Figure 5C as published. The representative propidium iodide (PI) staining photo of the MSC-siHDAC1 group is incorrect. This photo was incorrectly chosen in the process of combining the figure. At the same time, we also reanalyzed the fluorescence intensity of PI. And, the results showed that MSCs-siHDAC1 more significantly decreased PI fluorescence intensity than that in the original article. The corrected Figure 5 appears below. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. ![file] , 
 Original figure, enhanced contrast: ![file] , 
 Dear Dr. Biskrensis, Thank you for your comment. When we found this error, we contact the editor of the journal immediately applying for correction and got feedback on September 9, 2019. Please see our corrigendum for Figure 5C in the Front. Cell. Neurosci. and Pubmed (PMID: 31537983). Also you can see the updated version of full text from link: https: www.frontiersin.org articles 10.3389 fncel.2018.00498 full. We do appreciate your concern to point out the problem. I believe you mentioned here was still the old version (PMID: 30662396). We apologize for the confusion it has caused. Yours sincerely, Shanshan Ma Also, please see our corrected Figure 5 with enhanced contrast: ![file] ,