Overexpression of microRNA-202-3p protects against myocardial ischemia-reperfusion injury through activation of TGF-β1/Smads signaling pathway by targeting TRPM6
Authors: Zhan-Ling Ni
Jian-Li Wu
Hui-Ying Wu
Journal: Cell Cycle (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: MicroRNA-202-3p; TGF-β1/Smads signaling pathway; TRPM6; myocardial ischemia/reperfusion injury; ventricular remodeling.
Affiliations: a Department of Cardiovascular Medicine , Fuwai Central China Cardiovascular Hospital , Zhengzhou , P.R. China., b Medical School , Huanghe S & T University , Zhengzhou , P.R. China.

Abstract:  MicroRNAs (miRNAs) have been found to act as key regulators in the pathogenesis of myocardial ischemic-reperfusion (I/R) injury. In this study, we explore the role and mechanism of microRNA-202-3p (miR-202-3p) in regulating cardiomyocyte apoptosis, in respective of the TGF-β1/Smads signaling pathway by targeting the transient receptor potential cation channel, subfamily M, member 6 (TRPM6). The targeting relationship between miR-202-3p and TRPM6 was verified by a dual-luciferase reporter gene assay. Sprague-Dawley rat models of myocardial I/R injury were initially established and treated with different mimics, inhibitors and siRNAs to test the effects of miR-202-3p and TRPM6 on myocardial I/R injury. The levels of inflammatory factors; IL-1β, IL-6, TNF-α as well as the degree of myocardial fibrosis and cardiomyocyte apoptosis were determined in rats transfected with different plasmids. TRPM6 was found to be the target of miR-202-3p. Up-regulated miR-202-3p or knockdown of TRPM-6 alleviated oxidative stress and inflammatory response, reduced ventricular mass, altered cardiac hemodynamics, suppressed myocardial infarction, attenuated cell apoptosis, and inhibited myocardial fibrosis. MiR-202-3p overexpression activates the TGF-β1/Smads signaling pathway by negatively regulating TRPM6 expression. Taken together, these findings suggest that miR-202-3p offers protection against ventricular remodeling after myocardial I/R injury via activation of the TGF-β1/Smads signaling pathway. 

Retracted: Yes

PubPeer comments:
 Fig 7c,  the gray values of TRPM6, TGF-u03b21, Bcl-2, Bax, Smad7, Smad2 and u03b2-actin protein bands in response to the treatment of miR-202-3p mimic, siRNA-TRPM6, miR-202-3p inhibitor or miR-202- 3p inhibitor + siRNA-TRPM6 . ![file] I am intrigued by the absence of background on this WB, and the way the bands remain perfectly linear and retain the shape of the protein blobs as they move up the gel. Is it possible for the authors to upload scans of the original gels? I compiled a montage of WBs from other papers that sample the same restricted morphological gamut: ![] --------------------- UPDATE: I should have followed the link to Supplementary Data, where the authors do provide originals for the WB: ![] ![] It is appears that the images for SMAD2 and SMAD2-p are from different gels, rather than from stripping and reblotting. , 
 Here are four line-ups of excised rodent hearts, subsequent to infarcts and myocardial ischaemic-reperfusion injuries. Clockwise from upper left: **Fig 4a from [Wu, Wu Ni (2019)] **,  photographs of [myocardial infarct size] in **rats** treated with miR-202-3p mimic, siRNATRPM6, miR-202-3p inhibitor or miR-202-3p inhibitor + siRNA-TRPM6 after 4 weeks (the white area was the infarction area) . Fig 2A from [Ge et al (2019)] :  myocardial tissues stained by TTC of **mice** treated with miR-26b agomir, miR-26b antagomir and or NS-398 (seven days after infarction). Fig 1A from [Zhao et al (2019)] .  TTC staining results revealed obvious IS in IRI **mice** (two weeks after infarction). Fig 5A from [Li et al (2019)] ,  Representative images of myocardial infarct in shamu2010operated and MI **rats** detected by triphenyltetrazolium chloride staining (seven days after infarction). ![] The same rough-textured surface appears throughout these images from different laboratories, allowing us to rescale them to a common scale: ![file] Two mouse hearts and two rat hearts are similar sizes. Is this correct? , 
 *[right]* Fig 4A again,  photographs of MIS in **rats** treated with miR-202-3p mimic, siRNATRPM6, miR-202-3p inhibitor or miR-202-3p inhibitor + siRNA-TRPM6 after 4 weeks . *[left]* Fig 1A from [Liu et al (2019)] .  The histopathology of myocardial tissues is reduced in MI RI **mice** with HTEB treatment. A... myocardial infarct size observed by TTC staining . Lightened and contrast-enhanced for clarity. ![] Overlap marked. Is it a heart from a mouse or a rat? Why is it in papers by two unrelated teams of authors? , 
 Retracted [17 March 2022] . ----------------------- We, the Editors and Publisher of the journal *Cell Cycle*, have retracted the following article: Hui-Ying Wu, Jian-Li Wu, and Zhan-Ling Ni. Overexpression of microRNA-202-3p protects against myocardial ischemia-reperfusion injury through activation of TGF-u03b21 Smads signaling pathway by targeting TRPM6. Cell Cycle. 2019;18(5):621-637. doi: 10.1080 15384101.2019.1580494. Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address the concerns raised and have not been able to provide their original data or supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. ,