miR-146a ameliorates liver ischemia/reperfusion injury by suppressing IRAK1 and TRAF6
Authors: Wenzhou Ding
Weiwei Jiang
Liyong Pu
Lianbao Kong
Guoqing Liu
Qingfeng Ni
Liangliang Kong
Yeting Lu
Weibing Tang
Journal: PLoS ONE (2014)
Discipline: Multidisciplinary
Keywords: Toll-like receptor; miR-146a; IRAK1; TRAF6; liver ischemia/reperfusion injury
Affiliations: Department of Neonatal Surgery, Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing, China., Department of Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Abstract:  A critical role of the Toll-like receptor(TLR) and its downstream molecules, including IL-1 receptor-associated kinase 1(IRAK1) and tumor necrosis factor receptor- associated factor 6(TRAF6), in the pathogenesis of liver ischemia/reperfusion (I/R) injury has been documented. Recently a microRNA, miR-146a, was identified as a potent negative regulator of the TLR signaling pathway. In this study, we investigated the role of miR-146a to attenuate TLR signaling and liver I/R injury in vivo and in vitro. miR-146a was decreased in mice Kupffer cells following hepatic I/R, whereas IRAK1 and TRAF6 increased. Overexpression of miR-146a directly decreased IRAK1 and TRAF6 expression and attenuated the release of proinflammatory cytokines through the inactivation of NF-κB P65 in hypoxia/reoxygenation (H/R)-induced macrophages, RAW264.7 cells. Knockdown experiments demonstrated that IRAK1 and TRAF6 are two potential targets for reducing the release of proinflammatory cytokines. Moreover, co-culture assays indicated that miR-146a decreases the apoptosis of hepatocytes after H/R. In vivo administration of Ago-miR-146a, a stable version of miR-146a in vivo, protected against liver injury in mice after I/R via inactivation of the TLR signaling pathway. We conclude that miR-146a ameliorates liver ischemia/reperfusion injury in vivo and hypoxia/reoxygenation injury in vitro by directly suppressing IRAK1 and TRAF6. 

Retracted: No

PubPeer comments:
 An image in Figure 6D and 6G appear to be the same, although described as if stained differently. Apologies if I am misunderstanding something. *** ![file] , 
 Dear reviewer Thank you very much for your careful review. We checked the original submission picture. The original submission picture was completed in October 2013 (the time can be seen in the attached picture). At that time, D2 was like this, not the published one. It should be that there was a mistake in copying the picture when revising the draft later. We apologize for the trouble we have caused you. We ll tell the magazine that the picture is wrong. Lianbaokong , 
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 #2 Thank you for your reply. , 
 Of note, I reported the same duplication to the journal in October 2015, but have not heard back. , 
 Dear reviewer Thank you very much for your careful review. We checked the original submission picture. The original submission picture was completed in October 2013 (the time can be seen in the attached picture). At that time, D2 was like this, not the published one. It should be that there was a mistake in copying the picture when revising the draft later. We apologize for the trouble we have caused you. We ll tell the magazine that the picture is wrong. Lianbaokong , 
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 #5 I ll contact the magazine to make corrections. Thank you very much again ,