Mir-21 Mediates the Inhibitory Effect of Ang (1–7) on AngII-induced NLRP3 Inflammasome Activation by Targeting Spry1 in lung fibroblasts

• Published in: Scientific reports Vol. 7; no. 1; pp. 14369 - 11
• Main Authors: Sun, Na-Na, Yu, Chang-Hui, Pan, Miao-Xia, Zhang, Yue, Zheng, Bo-Jun, Yang, Qian-Jie, Zheng, Ze-Mao, Meng, Ying
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 30.10.2017; Nature Publishing Group
• Subjects: 13/1; 13/109; 13/2; 13/21; 13/31; 13/44; 13/51; 13/95; 38/32; 38/35; 631/337/384/331; 631/443/1784; ACE2; Angiotensin; Angiotensin I - genetics; Angiotensin I - pharmacology; Angiotensin II; Angiotensin II - metabolism; Angiotensin-converting enzyme 2; Animals; Apoptosis; Apoptosis - drug effects; Bleomycin; Bleomycin - adverse effects; Cells, Cultured; Collagen; Collagen Type I - metabolism; Fibroblasts; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - physiology; Fibrosis; Humanities and Social Sciences; Inflammasomes; Inflammasomes - genetics; Inflammasomes - metabolism; Lung - metabolism; Lung diseases; Male; MAP Kinase Signaling System - drug effects; MicroRNAs - genetics; MicroRNAs - metabolism; MicroRNAs - physiology; miRNA; multidisciplinary; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - physiology; NF-kappa B - metabolism; NF-κB protein; NLR Family, Pyrin Domain-Containing 3 Protein - genetics; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; Overexpression; Peptide Fragments - genetics; Peptide Fragments - pharmacology; Peptide Hormones - metabolism; Peptidyl-dipeptidase A; Pulmonary fibrosis; Pulmonary Fibrosis - metabolism; Rats; Rats, Wistar; Rodents; Science; Science (multidisciplinary); Signal Transduction - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-13305-3

MicroRNA-21 (mir-21) induced by angiotensin II (AngII) plays a vital role in the development of pulmonary fibrosis, and the NLRP3 inflammasome is known to be involved in fibrogenesis. However, whether there is a link between mir-21 and the NLRP3 inflammasome in pulmonary fibrosis is unknown. Angiotensin-converting enzyme 2/angiotensin(1–7) [ACE2/Ang(1–7)] has been shown to attenuate AngII-induced pulmonary fibrosis, but it is not clear whether ACE2/Ang(1–7) protects against pulmonary fibrosis by inhibiting AngII-induced mir-21 expression. This study’s aim was to investigate whether mir-21 activates the NLRP3 inflammasome and mediates the different effects of AngII and ACE2/Ang(1–7) on lung fibroblast apoptosis and collagen synthesis. In vivo , AngII exacerbated bleomycin (BLM)-induced lung fibrosis in rats, and elevated mir-21 and the NLRP3 inflammasome. In contrast, ACE2/Ang(1–7) attenuated BLM-induced lung fibrosis, and decreased mir-21 and the NLRP3 inflammasome. In vitro , AngII activated the NLRP3 inflammasome by up-regulating mir-21, and ACE2/Ang(1–7) inhibited NLRP3 inflammasome activation by down-regulating AngII-induced mir-21. Over-expression of mir-21 activated the NLRP3 inflammasome via the ERK/NF-κB pathway by targeting Spry1, resulting in apoptosis resistance and collagen synthesis in lung fibroblasts. These results indicate that mir-21 mediates the inhibitory effect of ACE2/Ang(1–7) on AngII-induced activation of the NLRP3 inflammasome by targeting Spry1 in lung fibroblasts.