Protective effects of Progranulin against focal cerebral ischemia‐reperfusion injury in rats by suppressing endoplasmic reticulum stress and NF‐κB activation in reactive astrocytes
Authors: Shi-Jun Li
Hua Fan
Qing Shu
Dan Zhou
Jun-Qiang Yan
Xiao-Yan Zhao
Gang Wu
Wei Ma
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Endoplasmic reticulum (ER) stress; astrocyte; focal cerebral ischemia-reperfusion; nuclear factor kappa B; progranulin (PGRN).
Affiliations: Department of PharmacyThe Ninth Hospital of Xi'anXi'anChina, The First Affiliated Hospital of Henan University of Science and TechnologyLuoyangChina, Department of PharmacyWuhan Union HospitalWuhanChina, The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina

Abstract:  The aim of this study is to explore the effect progranulin (PGRN) has on endoplasmic reticulum (ER) stress and the NF-κB activation in reactive astrocytes found in rat models with focal cerebral ischemia-reperfusion (I/R) injury. Sprague-Dawley (SD) rats were grouped into the sham, I/R, PGRN-high dose, PGRN-low dose, and negative control (NC) groups. TTC staining was applied in order to detect the cerebral infarction volume, a TUNEL assay to detect the apoptosis rate of neurons, an ELISA to measure MDA, SOD, iNOS, LDH, TNF-α, IL-1β, IL-6, and IL-10 levels, and both RT-qPCR and western blotting methods in order to detect PGRN, GFAP, GRP78, CHOP, and NF-κB p65 expressions. The astrocytes (AST) cells were then assigned into the normal, I/R, negative control (NC), PGRN-high dose, and PGRN-low dose groups. After completing the transfection process, the proliferative capacity of AST cells was detected by use of the CCK-8 assay. Both the in vivo and in vitro results, in comparison with the I/R and the NC groups, the PGRN-high dose and PGRN-low dose groups both presented a decrease in cerebral infarction volume, apoptosis rate of neurons, MDA, LDH, iNOS, TNF-α, IL-1β, IL-6 levels, and GFAP, GRP78, CHOP, NF-κB p65 expressions, and an increase in SOD, IL-10, and PGRN levels as well as cell proliferation depending on dosage. Based on our results, we came to the confirmation that PGRN can reduce neuronal apoptosis by mitigating ER stress in the reactive astrocytes as well as downregulating the inflammatory levels by suppressing the NF-κB signaling pathway. 

Retracted: Yes

PubPeer comments:
 Fig 4B.  histogram of Nissl staining and cell number of neurons among the sham, I R, NC and PGRN-high dose, and PGRN-low dose groups . PGRN-high-dose image is an enlarged detail of PGRN-low-dose image. Perhaps dose is a translation error, and the word  enlargement was intended. ![file] Orange box encloses an area of image that also appears in Fig 3B of [Han et al (2018)] , albeit horizontally-flipped. ![file] , 
 Clockwise from upper left: Figs 2B, 6B, 9B. Evidently not a concern for the reviewers that the same beta-actin loading control has been used with two different PGRN bands. ![file] Of course the reviewers were not to know that the same loading controls had recently featured in Figs 2C and 10D of [Zhang et al (2018)] , though there labeled GAPDH . ![] Not to mention dozens of other appearances in this oeuvre of work, possibly the output of a papermill. For comparison, Figs 5B and 11B from [Fan et al (2018)] . ![] Further examples occupy a Google document: https: docs.google.com spreadsheets d 1r0MyIYpagBc58BRF9c3luWNlCX8VUvUuPyYYXzxWvgY edit?usp=sharing , 
 Retracted [21 July 2021] . ---------------------------------------- The above article, published online on 17 April 2018 in Wiley Online Library has been retracted by agreement between the the authors, 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. The conclusions of this article are invalid. ,