Activation of the mammalian target of rapamycin signaling pathway underlies a novel inhibitory role of ring finger protein 182 in ventricular remodeling after myocardial ischemia‐reperfusion injury
Authors: Zhi-Feng Wei
Yan-Li Gao
Jing-Hui Sun
Jing-Hua Wang
Cong-Cong Liu
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: gene silencing; mammalian target of rapamycin (mTOR) signaling pathway; myocardial ischemia-reperfusion injury (MIRI); ring finger protein 182 (RNF182); ventricular remodeling.
Affiliations: Department of Pediatric Rheumatology, Immunology and Allergy, The First Hospital of Jilin University, Changchun, China., Department of Cardiology, FAW General Hospital, Changchun, China., Department of Science and Education, The First Hospital of Jilin University, Changchun, China., Department of Pediatric Cardiology, The First Hospital of Jilin University, Changchun, China.

Abstract:  Myocardial ischemia-reperfusion injury (MIRI) is a major cause of cardiovascular disease, leading to mortality and disability associated with coronary occlusion worldwide. A correlation of mammalian target of rapamycin (mTOR)/nuclear factor-kappa B (NF-κB) signaling pathway has been observed with brain damage resulting from myocardial ischemia. Therefore, by establishing MIRI rat model, this study aimed to explore whether ring finger protein 182 (RNF182) regulates the mTOR signaling pathway affecting MIRI. Initially, MIRI rat model was successfully established, followed by either treatment of shRNF182 or phosphoesterase (PITE) (inhibitor of the mTOR signaling pathway). Then, the serum levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA), left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular systolic pressure (LVSP), and left ventricular end-diastolic pressure (LVEDP) were determined, followed by detection of myocardial infarct sizes and myocardial cell apoptosis. Moreover, the levels of related genes/proteins were determined to further determine the mechanisms of RNF182 in MIRI. First, RNF182 was upregulated in MIRI. Another key observation of this study was that rats with shRNF182 presented with downregulated SOD, GSH-Px, and MDA in serum, accompanied by decreased levels of LVEF, LVFS, LVSP, and LVEDP. In addition, both reduced myocardial infarct sizes and apoptosis of myocardial cells were observed after silencing RNF182. Furthermore, silencing of the RNF182 was observed to downregulate Bcl 2-associated X and cysteine proteinase 3 but upregulate mTOR, ribosome protein subunit 6 kinase 1, eukaryotic elongation factor 2, and B-cell lymphoma-2. Importantly, the effects of RNF182 silencing were reversed after PITE treatment. In conclusion, our study demonstrates that RNF182 silencing can prevent ventricular remodeling in rats after MIRI by activating the mTOR signaling pathway. 

Retracted: No

PubPeer comments:
 ![file] Figure 3, the Blank and NC group pictures seem to originate from the same picture. If it is the author s error, I hope they can correct it as soon as possible. , 
 Fig 2A,  The infarct ischemic areas in each group . I am sure that these slices of ischemia-damaged rat brains are 100% unretouched, but the problem remains that they are illustrating a paper about ischemia-damaged rat **hearts**. ![file] , 
 Fig 4C,  gray value of RNF182, Bax, caspaseu20103, mTOR, S6K1, eEF2, Bclu20102, pu2010mTOR, pu2010S6K1, and pu2010eEF2 protein bands determined by Western blot analysis . ![file] Here is a montage of curious Western Blots I collected, representing the same distinct style. They are marked by high contrast and an absence of any background texture, and resemble ink blobs. They are not always sharp-edged; sometimes the ink appears to have spread, creating filaments. When there are double bands (ERK 1 2, JNK 1 2, LC3 I II, the sub-bands are somehow decoupled: differing in overall profile and in the width of the protein blobs, and with horizontal displacements, almost falling into different lanes. The papers that contain them tend to be problematic in other ways (some have been retracted). Their manifestations began in 2019 papers, and stopped in 2020 as if their use became deprecated. ![] Sources include - [He et al (2020)] - [Chang et al (2020)] - [Shang et al (2020)] - [Shi et al (2019)] *[RETRACTED]* - [Xu et al (2019)] *[RETRACTED]* - [Jia et al (2020)] - [Feng et al (2019)] Examples could be multiplied but I will settle for three more examples, to show the range of this gamut, from - [Qu et al (2019)] *[RETRACTED]* - [Song et al (2019)] *[RETRACTED]* - [Shi et al (2019)] . ![file] ,