MicroRNA-370 protects against myocardial ischemia/reperfusion injury in mice following sevoflurane anesthetic preconditioning through PLIN5-dependent PPAR signaling pathway
Authors: Jin-Quan Chen
Ji-Xue Mu
Run-Gang Shan
Li-Jun Zhang
Juan Zhao
Zhen-Zhong Sun
Yan-Bin Zhao
Kai Wang
Journal: Biomedicine & Pharmacotherapy (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: MicroRNA-370; Myocardial ischemia/reperfusion injury; Perilipin-5; Peroxisome proliferator activated-receptor signaling pathway; Preconditioning
Affiliations: Department of Anesthesiology, the First Hospital of the PLA, Lanzhou 730031, PR China., Department of Anesthesiology, the First Hospital of Lanzhou University, Donggang Courtyard Area, Lanzhou 730030, PR China., Department of Anesthesiology, Lanzhou Time Laser Cosmetic Surgery Hospital, Lanzhou 730030, PR China., Department of Anesthesiology, Guangdong Armed Police Corps Hospital, Guangzhou 510507, PR China., Department of Anesthesiology, the First People's Hospital of Xianyang City, Xianyang 712000, PR China. Electronic address: ., Lanzhou Minimally Invasive Orthopedic Hospital, Lanzhou 730050, PR China. Electronic address: .

Abstract:  Myocardial ischemia/reperfusion injury (IRI) has long been identified to be a contributor to adverse cardiovascular outcomes following myocardial ischemia, cardiac surgery or circulatory arrest. This study aims to investigate the effects of microRNA (miR-370) targeting perilipin-5 (PLIN5) in mice following sevoflurane anesthetic preconditioning (SAP). A mouse model of left ventricular myocardial IRI was established, followed by the evaluation of myocardial infarction size and cardiac function to determine the effects of SAP. The underlying regulatory mechanisms of miR-370 were analyzed in concert with the treatment of miR-370 mimic, miR-370 inhibitor, or siRNA against PLIN5 in cardiomyocytes isolated from mice with IRI. Also, cardiomyocyte proliferation, cell cycle distribution and apoptosis were evaluated following treatment. Lastly, SAP-treated I/R mice were injected with miR-370 inhibitor to verify the mechanism of SAP. The use of SAP conferred cardioprotective effects on myocardial IRI. MiR-370 was downregulated in mice that exhibited IRI, but SAP elevated the miR-370 expression. Functionally, miR-370 negatively targeted PLIN5 and activated the peroxisome proliferator activated-receptor (PPAR) signaling pathway, leading to decreased PPARγ expression but increased PPARα expression. The results also showed that elevation of miR-370 or the silencing of PLIN5 promoted cardiomyocyte proliferation. miR-370 also inhibited cardiomyocyte apoptosis as reflected by decreased caspase-3 expression and increased Bcl-2 expression. Additionally, SAP also alleviated I/R injury by inhibiting PPARγ. This study demonstrates that SAP induces miR-370 and exerts cardioprotective effects on myocardial IRI, where upregulation of miR-370 alleviates myocardial IRI via inhibiting the PLIN5-dependent PPAR signaling pathway. 

Retracted: No

PubPeer comments:
 Fig 8A.  PI-stained cardiomyocytes at the G0 G1, S, and G2 M phases. Enlarged insets are mine. ![file] These cell-cycle plots make no sense. They appear to be hand-drawn by someone with a vague idea of what flow-cytometry analyses should look like. As well as a wiggly line (raw data histogram), each panel contains a smoother line, which is supposed to be the sum of the red peaks and the hatched hump (G0 G1, G2 M, S components). Clearly, though, the smooth line are **not** the sums of those components. , 
 Here is a montage of curious Western Blots I collected, representing a 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] ---------------------------------------------- Here are the present 4B, 6B:  the relative protein expression of PLIN5, PPARu03b1, PPARu03b3, Bcl-2 and caspase-3, as detected by western blot analysis . They appear to be manifestations of the same style. Is it possible for the authors to upload or link to scans of the original blots, to allay any concerns? ![file] ,