The angiotensin-converting enzyme 2/angiotensin (1–7)/mas axis protects against pyroptosis in LPS-induced lung injury by inhibiting NLRP3 activation
Authors: Jin Wang
Haihua Huang
Fengying Gao
Zhenwei Liu
Journal: Archives of Biochemistry and Biophysics (2020)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: ACE2; Acute lung injury; Ang(1–7); Mas; NLRP3
Affiliations: Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, PR China., Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200080, PR China. Electronic address: ., Department of Respiratory Medicine, Shanghai Construction Group Hospital, Shanghai, 200083, PR China. Electronic address: .

Abstract:  Previous studies have suggested that pyroptosis may play an important role in LPS-induced acute lung injury (ALI), but the exact mechanism of pyroptosis induction and the role of Angiotensin-converting enzyme 2 (ACE2)/Ang (1-7)/Mas axis in pyroptosis has not been investigated yet. The present study aimed to establish a mice model of ALI and clarify the involvement of pyroptosis and ACE2/Ang (1-7)/Mas axis. The results showed that LPS induced pyroptosis in lung, demonstrated by increased expression of Gasdermin D (GSDMD), cleaved GSDMD, IL-1β, and Caspase-1. Treatment of Ang (1-7) significantly reduced the severity of ALI and pyroptosis, while AngII significantly exaggerated them. Furthermore, ACE2 activator resorcinolnaphthalein (RES) significantly reduced the severity of ALI and pyroptosis, but ACE2 inhibitor MLN-4760 and Mas inhibitor A779 significantly exaggerated them, suggesting that the ACE2/Ang (1-7)/Mas axis was involved in the pyroptosis in LPS-induced ALI. In addition, Ang (1-7) and RES significantly decreased the levels of NLRP3, which were increased by AngII and A779. NLRP3 knockout significantly reduced the severity of ALI and pyroptosis. In conclusion, pyroptosis played an important role in ALI induced by LPS. The ACE2/Ang (1-7)/Mas axis negatively regulated the pyroptosis and protected mice against LPS-induced ALI through NLRP3 inhibition. The present study expanded our understating of the role of ACE2/Ang (1-7)/Mas axis in ALI by providing a novel explanation that it may regulate the pyroptosis in ALI. 

Retracted: No

PubPeer comments:
 Another in a series of  Travelling Ruler posts. These six line-ups of xenograft tumors came from different research teams at different institutions, but somehow they seem to use the same ruler to provide scale. Fig 1J from [Zhang, Long Hu (2020)] . Representative images of the tumor xenografts obtained from groups u201csh-LINC00205u201d and u201csh-NCu201d. ![file] **Fig 7B from [Liu et al (2020)] **.  Images of tumor xenografts derived from sh-OSER1-AS1 or sh-NC-stably transected H522 cells . ![file] Fig 7B from [Yang et al (2020)] .  After 4 weeks, all the mice were euthanized, and the tumor xenografts were excised and photographed. ![file] Fig 6B of [Xing et al (2020)] .  The tumor xenografts obtained from sh-LINC01224 or sh-NC groups. ![file] Fig 6B from [Qi, Lu Wang (2020)] .  Representative photograph of tumor xenografts obtained from the sh-ST7-AS1 and sh-NC groups . ![file] Fig 7C from [Hou, Dong Du (2020)] .  Tumor xenografts representative images collected from groups u2018shLINC00466u02b9 and u2018sh-NCu2019. ![file] Of course there are a lot of metal rulers of any given brand within laboratories, but the pattern of smudges and mottling on these six is similar enough to suggest identity. ![file] ,