Instillation of particulate matter 2.5 induced acute lung injury and attenuated the injury recovery in ACE2 knockout mice

• Published in: International journal of biological sciences Vol. 14; no. 3; pp. 253 - 265
• Main Authors: Lin, Chung-I, Tsai, Chin-Hung, Sun, Yu-Ling, Hsieh, Wen-Yeh, Lin, Yi-Chang, Chen, Cheng-Yi, Lin, Chih-Sheng
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2018; Ivyspring International Publisher
• Subjects: ACE2; ACE2 gene; Angiotensin; Angiotensin II; Angiotensin-converting enzyme 2; Animal models; Cytokines; Enzymes; Inflammatory response; Injuries; Lung diseases; Lungs; Mice; Particulate matter; Pathogenesis; Peptidyl-dipeptidase A; Renin; Research Paper; Respiration; Respiratory rate; Rodents; Signaling; Stat3 protein; Trachea; particulate matter 2.5; inflammation; acute lung injury; renin-angiotensin system; angiotensin-converting enzyme II
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.23489

Inhaled particulate matter 2.5 (PM ) can cause lung injury by inducing serious inflammation in lung tissue. Renin-angiotensin system (RAS) is involved in the pathogenesis of inflammatory lung diseases and regulates inflammatory response. Angiotensin-converting enzyme II (ACE2), which is produced through the angiotensin-converting enzyme (ACE)/angiotensin II (Ang II) axis, protects against lung disease. However, few studies have focused on the relationships between PM and ACE2. Therefore, we aimed to explore the role of ACE2 in PM -induced acute lung injury (ALI). An animal model of PM -induced ALI was established with wild type (C57BL/6, WT) and ACE2 gene knockout (ACE2 KO) mice. The mice were exposed to PM through intratracheal instillation once a day for 3 days (6.25 mg/kg/day) and then sacrificed at 2 days and 5 days after PM instillation. The results show that resting respiratory rate (RRR), levels of inflammatory cytokines, ACE and MMPs in the lungs of WT and ACE2 KO mice were significantly increased at 2 days postinstillation. At 5 days postinstillation, the PM -induced ALI significantly recovered in the WT mice, but only partially recovered in the ACE2 KO mice. The results hint that PM could induce severe ALI through pulmonary inflammation, and the repair after acute PM postinstillation could be attenuated in the absence of ACE2. Additionally, our results show that PM -induced ALI is associated with signaling p-ERK1/2 and p-STAT3 pathways and ACE2 knockdown could increase pulmonary p-STAT3 and p-ERK1/2 levels in the PM -induced ALI.