Knocking down PFL can improve myocardial ischemia/reperfusion injury in rats by up-regulating heat shock protein-20
Authors: H You
J Shen
F-L Ye
W-X Gu
Y-M Wu
R-L Yin
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: lncRNA; PFL; myocardial ischemia/reperfusion injury; rats; myocardial infarction
Affiliations: Department of Cardiology, the Wujiang Affiliated Hospital of Nantong University, Suzhou, China. .

Abstract:  Objective: To investigate the effect and mechanism of long non-coding ribonucleic acid (lncRNA) PFL on myocardial ischemia/reperfusion (I/R) injury in rats, and to provide a reference for the prevention and treatment of myocardial infarction (MI) in clinic. Materials and methods: According to the random number table, 60 male Sprague-Dawley (SD) rats were randomly divided into 3 groups: Control group (n=20), I/R group (n=20), and I/R + PFL small interfering ribonucleic acid (siRNA) group (n=20). The I/R model was established by ligating the left anterior descending coronary artery (LAD) and then recanalizing it. PFL siRNAs were injected intravenously into the tail vein of rats in I/R + PFL siRNA group to construct a PFL knockout model. Triphenyl tetrazolium chloride (TTC) test was used to detect the infarction area of each group. Echocardiography was adopted to measure the ejection fraction [EF (%)] and fraction shortening [FS (%)] of rats in each group. Hematoxylin and eosin (H&amp;E) staining was applied to detect the morphological changes in myocardial cells in each group. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was conducted to detect the apoptosis levels of myocardial cells and fibroblasts in heart tissues in each group. Meanwhile, the protein expression levels of apoptosis-related genes, Bcl-2-associated X protein (BAX), and Bcl-2, were measured via Western blotting. Also, the expression level of heat shock protein 20 (HSP-20) in the heart of three groups of rats was examined using immunohistochemical staining. Finally, the effects of PFL siRNAs on the expression level of HSP-20 were detected via Western blotting. Results: PFL siRNAs could significantly improve I/R-induced cardiac insufficiency in rats, thus increasing EF (%) and FS (%) (p&lt;0.05). Besides, PFL siRNAs could remarkably inhibit cardiac infarction caused by I/R injury and reduce the infarction area from (59.54¬±3.45)% to (24.85¬±1.30)% (p&lt;0.05). H&amp;E staining results manifested that, compared with those in I/R group, the cardiac myofilament was better in alignment, degradation and necrosis were milder, and cell edema was notably reduced in I/R + PFL siRNA group. Immunohistochemistry and Western blotting results showed that PFL siRNAs could remarkably reverse the decrease in the HSP-20 expression caused by I/R (p&lt;0.05). Conclusions: We found that PFL knockdown can significantly improve the myocardial injury caused by I/R and improve the cardiac function in rats. The mechanism may be related to the activation of HSP-20 by PFL siRNAs. Therefore, PFL is expected to become a new target for the treatment of MI. 

Retracted: Yes

PubPeer comments:
 Figure 5.  H E staining results of the heart of rats in each group. Control: Control group, I R: I R group and I R + PFL siRNA: I R + PFL knockdown group.  Please compare with Figure 5 from [Sun et al (2019)] .  H E staining results in each group (magnification: 100u00d7). Control: Control group, I R: ischemia-reperfusion group, I R+MALAT1 siRNA: ischemia-reperfusion + MALAT1 knockdown group.  , 
 In the section of Materials and Methods, under the heading of  Triphenyl Tetrazolium Chloride (TTC) Staining , the authors described the TTC staining protocol for fresh brain tissue samples. But the brain tissue staining results were not mentioned or discussed there after. In their Results section, however, under the heading of  Knocking down PFL reduced the MI area in I R rats , the TTC staining results were referred as the infarction area of the heart. Were any brain samples collected and stained by using TTC? If so, for what purpose in this myocardial infarction study? Or, when the authors described the TTC staining protocol, they actually meant  heart tissue rather than  brain tissue ? I would appreciate an explanation from the author. , 
 Withdrawn. https: www.europeanreview.org article 23554 *The article u201cKnocking down PFL can improve myocardial ischemia reperfusion injury in rats by up-regulating heat shock protein-20, by R.-L. Yin, H. You, Y.-M. Wu, F.-L. Ye, W.-X. Gu, J. Shen, published in Eur Rev Med Pharmacol Sci 2019; 23 (17): 7619-7627u2013DOI: 10.26355 eurrev_201909_18885u2013PMID: 31539154u201d has been withdrawn from the authors since u201cdue to some inaccuracies (some data cannot be repeated by our further research)u201d.* *The Publisher apologizes for any inconvenience this may cause.* , 
 Fig 5:  These panels appear to have been pilfered from Fig 1A of  Gypenoside Protects Cardiomyocytes against Ischemia-Reperfusion Injury via the Inhibition of Mitogen-Activated Protein Kinase Mediated Nuclear Factor Kappa B Pathway In Vitro and In Vivo ([Yu et al 2016] ).  Presumably whoever wrote [Sun et al 2019] copied from the same source. , 
 *[above]* Fig 4. Plagiarised from *[below]* Fig 1G of  Eriodictyol Attenuates Myocardial Ischemia-Reperfusion Injury through the Activation of JAK2 ([Li et al 2018] ).  , 
 *[above]* Fig 6. Taken from *[below]* Fig 3A of Li et al (2018).  , 
 *[left]* Fig 3. Previously published as *[right]* Fig 5A of  miR-125a, miR-139 and miR-324 contribute to Urocortin protection against myocardial ischemia-reperfusion injury ([Du00edaz et al 2017] ).  , 
 #1 The text of the present paper is also close to [Sun et al (2019)] . A colleague compared them with SimTexter  That is comparing the opening paragraphs. The Conclusions differ more, as they describe different treatments.  ---------------------- #2 * In the section of Materials and Methods, under the heading of  Triphenyl Tetrazolium Chloride (TTC) Staining , the authors described the TTC staining protocol for fresh brain tissue samples. But the brain tissue staining results were not mentioned or discussed there after. * *O. buddha s* question about  brain tissues did receive a reply... not in this thread, oddly enough, but in the thread devoted to [Sun et al 2019] , and purportedly signed by Tao Sun (that paper s first author). And we also reviewed the description regarding the TTC of fresh brain, if we not omit, we mention the myocardial not brain tissue throughout the paper in the Method and Result section. One can be forgiven for suspecting that both papers are the work of a single papermill, using fake email addresses to submit the manuscripts, and unable to keep the multiple identities and comment threads straight. ,