Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways
Authors: Mengfan Liang
Ming Zhou
Yujing Liu
Yongmei Cao
Zhen Zeng
Caihua Xi
Ying Xue
Wei Jiang
Yingchuan Li
Feng Ping
Journal: Scientific Reports (2016)
Discipline: Multidisciplinary
Keywords: Acute respiratory distress syndrome (ARDS); ACE2; lung injury; MAPKs; NF-κB signaling pathway
Affiliations: Department of Anesthesiology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, China.

Abstract:  Acute respiratory distress syndrome (ARDS) caused by severe sepsis remains a major challenge in intensive care medicine. ACE2 has been shown to protect against lung injury. However, the mechanisms of its protective effects on ARDS are largely unknown. Here, we report that ACE2 prevents LPS-induced ARDS by inhibiting MAPKs and NF-κB signaling pathway. Lentiviral packaged Ace2 cDNA or Ace2 shRNA was intratracheally administrated into the lungs of male SD rats. Two weeks after gene transfer, animals received LPS (7.5 mg/Kg) injection alone or in combination with Mas receptor antagonist A779 (10 μg/Kg) or ACE2 inhibitor MLN-4760 (1 mg/Kg) pretreatment. LPS-induced lung injury and inflammatory response were significantly prevented by ACE2 overexpression and deteriorated by Ace2 shRNA. A779 or MLN-4760 pretreatment abolished the protective effects of ACE2. Moreover, overexpression of ACE2 significantly reduced the Ang II/Ang-(1-7) ratio in BALF and up-regulated Mas mRNA expression in lung, which was reversed by A779. Importantly, the blockade of ACE2 on LPS-induced phosphorylation of ERK1/2, p38 and p50/p65 was also abolished by A779. Whereas, only the ERK1/2 inhibitor significantly attenuated lung injury in ACE2 overexpressing rats pretreated with A779. Our observation suggests that AEC2 attenuates LPS-induced ARDS via the Ang-(1-7)/Mas pathway by inhibiting ERK/NF-κB activation. 

Retracted: No

PubPeer comments:
 Figure 5B. Much more similar and different than expecyed. ![file] , 
 For this figure, we have done several sets of experiments: - experiments comparing Parental with DoxoR ; - experiments comparing siZRANB2 with DoxoR siCtl ; - and experiments comparing siSYF2 with DoxoR siCtl . We have repeated all these experiments several times. In the figure, for MAST2, the 3 samples labelled DoxoR or DoxoR siCtl come from different sets of experiments, thus explaining why they look different. In fact, they are not so much different, because what is important is the relative abundance of the two isoforms, rather than the overall signal intensity. Another key point is that the different conditions located in a same box (for example, Parental and DoxoR ) were tested in parallel. The idea here is to compare the isoform ratio between conditions. The same thing goes for ECT2. For MRPL55, the reason why the lanes labeled DoxoR and DoxoR siCtl look identical is that they are indeed identical. This is because on that day, all the conditions were tested in parallel, thus the control was done only once. For simplicity, to keep the figure organization in 3 boxes as for MAST2 and ECT2, we had to show this control 3 times. As it is quite obvious in this figure that the 3 boxes are not replicates of each other (they are dealing with different test conditions: siZRANB2, siSYF2 and Parental), I think it is not misleading. (The other option would be to show the control only once, together with all the other conditions (siZRANB2, siSYF2 and Parental) in a single box; but this would make the whole figure more complicated to read, because the organization of samples would be different than for MAST2 and ECT2.) , 
 https: retractionwatch.com 2021 05 28 imperial-college-london-researcher-fired-for-research-misconduct , 
 #3 Thank you for this information. In our paper, the contribution of Eric Lam was to provide the MCF7-DoxoR cell line (as mentioned in the acknowledgements section). This cell line was previously published (ref. 20) and we verified that it is highly resistant to doxorubicin. ,