Inhibitory role of lentivirus‐mediated aquaporin‐4 gene silencing in the formation of glial scar in a rat model of traumatic brain injury
Authors: Yu-Ming Li
Chuan-Ming Luo
Ke Han
De-Xia Zhong
Ya-Xiong Yong
Jia Lian
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: aquaporin-4 (AQP4); gene silencing; glial scar; traumatic brain injury (TBI).
Affiliations: Department of Neurology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China., Department of Neurosurgery, First Affiliated Hospital of Guizhou Medical University, Guiyang, China.

Abstract:  Traumatic brain injury (TBI), an acute degenerative pathology of the central nervous system, is a leading cause of death and disability. As the glial scar is a mechanical barrier to nerve regeneration, inhibitory molecules in the forming scar and methods to overcome them have suggested molecular modification strategies to allow neuronal growth and functional regeneration. Herein, we aim to investigate the effects of aquaporin-4 (AQP4) gene silencing on the glial scar formation after TBI by establishing rat models. After modeling, TBI rats were transfected with AQP4 small hairpin RNA [shRNA] (AQP4 gene silencing by lentiviral vector-delivered shRNA) and empty vectors, respectively. Neurological functions of the rats were evaluated after TBI. The hematoxylin and eosin staining was conducted to observe histomorphological changes in rat brain tissues. The messenger RNA (mRNA) and protein expressions of glial fibrillary acidic protein (GFAP), vimentin, fibronectin, laminin, and AQP4 were measured by reverse transcription-quantitative polymerase chain reaction and Western blot analysis. The ratio of positive expression area was calculated, and the glial scar was observed by immunohistochemistry. At the 7th, 14th, and 28th days after TBI, TBI rats treated with AQP4 shRNA showed improved neurological function and lessened histomorphological changes. AQP4 gene silencing mediated by lentivirus decreased the mRNA and protein expressions of GFAP, vimentin, fibronectin, and laminin, the number of positive cells, the ratio of positive expression area, and the glial scar. Our study demonstrates that lentivirus-mediated AQP4 gene silencing could inhibit the formation of glial scar after TBI, which is beneficial to the recovery of neurological function. 

Retracted: Yes

PubPeer comments:
 Fig 3F.  Western blot analysis reveals that rats treated with AQP4 shRNA have reduced protein expressions of AQP4, GFAP, Vimentin, Fibronectin, and Laminin at the 7th, 14th, and 28th days after TBI ... F, Western blot bands showing the protein expressions of AQP4, GFAP, Vimentin, Fibronectin, and Laminin in the four groups . ![file] The presence of some familiar bands and protein blobs are suggestive of a papermill provenance for this Figure. Here, Fig 3A of [Huang et al (2017)] and Fig 5(a) of [Gao et al (2018)] . ![] Fig 8(a) of [Wu et al (2018)] . ![] , 
 Retracted [19 July 2021] . ---------------------------------------------- The above article, published online on 23 September 2018 in Wiley Online Library has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Christian Behl, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. , 
 This research work is a personal behavior and has nothing to do with Sun Yat sen University. The Western blot involved in the article was completed by a third party entrusted by me. I am deeply sorry for the failure to fulfill the obligation of data review and screening, which led to problems in the conclusion of the article. , 
 #3 Could you please tell us the name of the third party? ,