MicroRNA-34a Promotes Endothelial Dysfunction and Mitochondrial-mediated Apoptosis in Murine Models of Acute Lung Injury
Authors: Mohd Shahid
Harpreet Singh
Nidhi Mahajan
Pragnya Das
Vineet Bhandari
Dilip Shah
Mohammad Afaque Alam
Freddy Romero
Journal: American Journal of Respiratory Cell and Molecular Biology (2019)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: acute lung injury; endothelial activation; miR-34a; mitochondrial-mediated apoptosis; p53 induction.
Affiliations: Department of Pediatrics, Drexel University College of Medicine, Philadelphia, Pennsylvania, Department of Biochemistry, Panjab University, India, Center for Translational Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, Department of Pharmaceutical Sciences, Chicago State University College of Pharmacy, Chicago, Illinois; and, Department of Physiology and Cell Biology, the Ohio State University Wexner Medical Center, Columbus, Ohio

Abstract:  Recent evidence has shown that microRNAs (miRs) are involved in endothelial dysfunction and vascular injury in lung-related diseases. However, the potential role of miR-34a in the regulation of pulmonary endothelial dysfunction, vascular injury, and endothelial cells (ECs) apoptosis in acute lung injury (ALI)/acute lung respiratory distress syndrome is largely unknown. Here, we show that miR-34a-5p was upregulated in whole lungs, isolated ECs from lungs, and ECs stimulated with various insults (LPS and hyperoxia). Overexpression of miR-34a-5p in ECs exacerbated endothelial dysfunction, inflammation, and vascular injury, whereas the suppression of miR-34a-5p expression in ECs and miR-34a-null mutant mice showed protection against LPS- and hyperoxia-induced ALI. Furthermore, we observed that miR-34a-mediated endothelial dysfunction is associated with decreased miR-34a direct-target protein, sirtuin-1, and increased p53 expression in whole lungs and ECs. Mechanistically, we show that miR-34a leads to translocation of p53 and Bax to the mitochondrial compartment with disruption of mitochondrial membrane potential to release cytochrome C into the cytosol, initiating a cascade of mitochondrial-mediated apoptosis in lungs. Collectively, these data show that downregulating miR-34a expression or modulating its target proteins may improve endothelial dysfunction and attenuate ALI. 

Retracted: Yes

PubPeer comments:
 Figure 3H. Much more similar than expected. https: imgur.com 851zUkp , 
 Figure 3I. Much more similar than expected. https: imgur.com nOYdkPt , 
 Figure 5H. Much more similar than expected. https: imgur.com 1B9MtW7 , 
 #2 Figure 3I. Different number of lanes per panel. https: imgur.com 1hJzpJD , 
 #1 Figure 3H continued. ASC panel. Left- and rightmost lanes very similar. https: imgur.com ex37ryW , 
 Figure 2I. Much more similar than expected. https: imgur.com JiLRFuu , 
 Figure 4B and 2I. Much more similar than expected (after vertical and horizontal re-sizing), although the treatments are different. https: imgur.com KUS9qWn , 
 more duplications when comparing Fig 2 and Fig 4 ![file] but also when comparing Fig 3 and Fig 5 ![file] , 
 more duplications when comparing Fig 2 and Fig 4 ![file] but also when comparing Fig 3 and Fig 5 ![file] , 
 2021 retraction. https: www.atsjournals.org doi 10.1165 rcmb.v64retraction6 The article u201cMicroRNA-34a Promotes Endothelial Dysfunction and Mitochondrial-mediated Apoptosis in Murine Models of Acute Lung Injuryu201d (1), published in the April 2019 issue of the Journal, has been retracted by Drs. Shah, Das, Alam, Romero, Singh, and Bhandari (the Journal has been unable to contact or has received no response from Drs. Mahajan and Shahid). It was discovered that anomalies exist in the Western blot images for IL-6, NOX4, and ASC in Figure 3H and that similarities exist in the GAPDH bands in Figures 4B and 2I. The authors stand behind the conclusions of the work but acknowledge that the above anomalies compromise the scientific integrity of the paper. The participating authors have agreed to the decision to retract this paper and they apologize to the Journal and its readers. 1.tShah D, Das P, Alam MA, Mahajan N, Romero F, Shahid M, Singh H, Bhandari V. Micro-RNA-34a promotes endothelial dysfunction and mitochondrial-mediated apoptosis in murine models of acute lung injury. Am J Respir Cell Mol Biol 2019;60:465u2013477. , 
 https: retractionwatch.com 2022 02 08 philadelphia-area-lung-researcher-up-to-six-retractions ,