MiR-122 regulates cell apoptosis and ROS by targeting DJ-1 in renal ischemic reperfusion injury rat models
Authors: X-H Qu
K Zhang
Journal: European Review for Medical and Pharmacological Sciences (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: PI3K/AKT signaling pathway; PTEN; DJ-1; miR-122; ischemic reperfusion injury
Affiliations: Department of Kidney Medicine, Affiliated Hospital of Jining Medical University, Jining, Shandong, China. .

Abstract:  Objective: Phosphatidylinositol 3-kinase/protein kinase B ((PI3K/AKT) signaling pathway plays a role in regulating cell survival and apoptosis. Phosphatase and tensin homologue deleted on chromosome ten (PTEN) can negatively regulate PI3K/AKT signaling pathway, while DJ-1 (Parkinson gene 7) can negatively regulate expression and function of PTEN. DJ-1-PTEN/PI3K/AKT signaling pathway plays a role in the regulation of ischemic reperfusion (IR) injury. Bioinformatics analysis showed that there was a targeted complementary binding site between microRNA-122 (miR-122) and 3'-UTR of DJ-1 mRNA. This study aimed to investigate the effects of miR-122 in regulating DJ-1-PTEN/PI3K/AKT signaling pathway and acute renal I-R injury. Materials and methods: Rat renal artery was clamped and restored after 30 min to establish renal IR injury model. Renal tissue samples were collected at 10 h and 20 h after operation. miR-122 and DJ-1 mRNA were detected with quantitative Real-time PCR (qRT-PCR). DJ-1 protein was tested by using Western blot. Blood urea nitrogen (BUN) and serum creatinine (SCr) were measured. Rat tubular epithelial cells, RRTEC, were cultured in vitro and divided into transfection (miR-NC group) and treatment group (miR-122 inhibitor group). IR treatment was performed after 72 h of transfection. DJ-1, PTEN, AKT, and phosphorylated AKT (p-AKT) were detected using Western blot. Cell apoptosis and reactive oxygen species (ROS) were measured with flow cytometry. Results: Compared with Sham group, blood BUN and SCr contents significantly increased (p &lt; 0.05), miR-122 level significantly elevated (p &lt; 0.05), while DJ-1 mRNA and protein markedly declined (p &lt; 0.05) in IR model rats. Compared with control group, I-R treatment significantly up-regulated miR-122 and PTEN expressions (p &lt; 0.05), decreased DJ-1 and p-AKT levels (p &lt; 0.05), and induced apoptosis and ROS production (p &lt; 0.05) in RRTEC cells. Transfection with miR-122 inhibitor markedly up-regulated DJ-1 expression (p &lt; 0.05), enhanced PTEN/PI3K/AKT pathway activity (p &lt; 0.05), and reduced apoptosis and ROS production (p &lt; 0.05). Conclusions: MiR-122 increased significantly, while DJ-1 declined significantly during renal I-R injury. Down-regulation of miR-122 markedly elevated DJ-1, enhanced PTEN/PI3K/AKT pathway activity, and inhibited apoptosis and ROS generation in rat renal tubular epithelial cells to alleviate IR injury. 

Retracted: Yes

PubPeer comments:
 This article has been withdrawn and the link to the PDF has been removed. The journal writes:  *Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, u201cMiR-122 regulates cell apoptosis and ROS by targeting DJ-1 in renal ischemic reperfusion injury rat models, by X.-H. Qu, K. Zhang, published in Eur Rev Med Pharmacol Sci 2018; 22 (24): 8830-8838u2013DOI: 10.26355 eurrev_201812_16651u2013PMID: 30575925u201d has been withdrawn. The Publisher apologizes for any inconvenience this may cause. * It is unfortunate, and not according to COPE guideline, that the journal has removed the PDF. Luckily, the PDF was captured by the WayBackMachine, and can be found here: https: web.archive.org web 20200210111107 https: www.europeanreview.org wp wp-content uploads 8830-8838.pdf It appears to be part of the Paper Mill #2, AKA the Paint It Black Paper Mill, described by Smut Clyde on Leonid Schneider s blog For Better Science: https: forbetterscience.com 2020 02 27 dark-satanic-papermills Here is part of Figure 4 as an illustration of the soft-focus Western blots and particular shape of the flow cytometry plots. ![file] , 
 The publishers have restored the PDF (watermarked), so kudos to them for that. ![file] , 
 A [report from the Affiliated Hospital of Jining Medical College] , from September 30 2021, reads as follows {thanks Google Translate): -------------------- 11. Zhang Kun of the Affiliated Hospital of Jining Medical College is the corresponding author of the paper  MiR-122 regulates cell apoptosis and ROS by targeting DJ-1 in renal ischemic reperfusion injury rat models . After investigation, the paper  MiR-122 regulates cell apoptosis and ROS by targeting DJ-1 in renal ischemic reperfusion injury rat models in the paper  MiR-122 regulates cell apoptosis and ROS by targeting DJ-1 in renal ischemic reperfusion injury rat models is found to be the corresponding author and Qu Xiaohan as the corresponding author and Qu Xiaohan as the corresponding author. problem. The Affiliated Hospital of Jining Medical College will deal with the relevant responsible persons as follows: 1. Give corresponding author Zhang Kun (1) order him to make an in-depth inspection; (2) order him to withdraw the manuscript of the paper involved; (3) cancel the five-year application for science and technology plan projects (special projects, funds, etc.), science and technology awards, science and technology projects Talent titles and other qualifications, from July 13, 2020 to July 12, 2025; (4) Cancellation of five-year postgraduate tutor application and appointment qualifications from July 13, 2020 to July 2025 12th; (5) Cancellation of three-year professional title promotion qualifications from July 13, 2020 to July 12, 2023; (6) Criticism is reported in the hospital. 2. Give the first author Qu Xiaohan (1) Order him to make an in-depth inspection; (2) Cancel the five-year application for science and technology plan projects (special projects, funds, etc.), science and technology awards, science and technology talent titles, etc., from July 2020 From July 13, 2025 to July 12, 2025; (3) Cancellation of five-year postgraduate tutor application and appointment qualifications from July 13, 2020 to July 12, 2025; (4) Cancellation for three years The qualification for professional title promotion starts from July 13, 2020 to July 12, 2023; (5) Criticism is reported in the hospital. ,