Suppression of microRNA‐342‐3p increases glutamate transporters and prevents dopaminergic neuron loss through activating the Wnt signaling pathway via p21‐activated kinase 1 in mice with Parkinson's disease
Authors: Yong-Jian Wang
Xin Wen
Bin Hu
Chun-Hui Sun
Jun Lu
Shan Wang
Shao-Hua Fan
Qun Shan
Gui-Quan Chen
Yuan-Lin Zheng
Dong-Mei Wu
Xin-Rui Han
Juan Zhuang
Min Shen
Meng-Qiu Li
Zi-Feng Zhang
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: PAK1; Parkinson's disease; Wnt signaling pathway; apoptosis; dopaminergic neuron
Affiliations: Key Laboratory for Biotechnology on Medicinal Plants of Jiangsu Province, School of Life Science, Jiangsu Normal University, Xuzhou, China., College of Health Sciences, Jiangsu Normal University, Xuzhou, China., School of Environment Science and Spatial Informatics, China University of Mining and Technology, Xuzhou, China., Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, School of Life Sciences, Huaiyin Normal University, Huaian, China., State Key Laboratory of Pharmaceutical Biotechnology, MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing University, Nanjing, China.

Abstract:  Development of effective therapeutic drugs for Parkinson's disease (PD) is of great importance. Aberrant microRNA (miRNA) expression has been identified in postmortem human PD brain samples, in vitro and in vivo PD models. However, the role of miR-342-3p in PD has been understudied. The study explores the effects of miR-342-3p on expression of glutamate (Glu) transporter, and dopaminergic neuron apoptosis and proliferation by targeting p21-activated kinase 1 (PAK1) through the Wnt signaling pathway in PD mice. After establishment of PD mouse models, gain- or loss-of-function assay was performed to explore the functional role of miR-342-3p in PD. Number of apoptotic neurons and Glu concentration was then determined. Subsequently, PC12 cells were treated with miR-342-3p mimic, miR-342-3p inhibitor, dickkopf-1 (DKK1), and miR-342-3p inhibitor + DKK1. The expression of miR-342-3p, PAK1, the Wnt signaling pathway-related and apoptosis-related genes, Glutamate transporter subtype 1 (GLT-1), l-glutamate/ l-aspartate transporter (GLAST), tyrosine hydroxylase (TH) was measured. Also, cell viability and apoptosis were evaluated. PD mice exhibited increased miR-342-3p, while decreased expression of PAK1, GLT-1, GLAST, TH, and the Wnt signaling pathway-related and antiapoptosis genes. miR-342-3p downregulation could promote expression of PAK1, the Wnt signaling pathway-related and antiapoptosis genes. GLT-1, GLAST, and TH as well as cell viability, but reduce cell apoptosis rate. The results indicated that suppression of miR-342-3p improves expression of Glu transporter and promotes dopaminergic neuron proliferation while suppressing apoptosis through the Wnt signaling pathway by targeting PAK1 in mice with PD. 

Retracted: Yes

PubPeer comments:
 Retracted [20 July 2021] . ---------------------------------------------- The above article, published online on 26 October 2018 in Wiley Online Library , has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. As several flaws and inconsistencies between results presented and experimental methods described were found, the editors consider the conclusions of this article to be invalid. ---------------------------------------------- This paper was not previously flagged in Pubpeer, but was included in [a spreadsheet dedicated to probable products of the  Contractor Papermill ] , on account of problematic Western Blots. ![file] ,