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Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway.
Am J Respir Cell Mol Biol. 2014 Apr; 50(4):723-36.AJ

Abstract

Accumulating evidence has demonstrated that up-regulation of the angiotensin (Ang)-converting enzyme (ACE)/AngII/AngII type 1 receptor (AT1R) axis aggravates pulmonary fibrosis. The recently discovered ACE2/Ang-(1-7)/Mas axis, which counteracts the activity of the ACE/AngII/AT1R axis, has been shown to protect against pulmonary fibrosis. However, the mechanisms by which ACE2 and Ang-(1-7) attenuate pulmonary fibrosis remain unclear. We hypothesized that up-regulation of the ACE2/Ang-(1-7)/Mas axis protects against bleomycin (BLM)-induced pulmonary fibrosis by inhibiting the mitogen-activated protein kinase (MAPK)/NF-κB pathway. In vivo, Ang-(1-7) was continuously infused into Wistar rats that had received BLM or AngII. In vitro, human fetal lung-1 cells were pretreated with compounds that block the activities of AT1R, Mas (A-779), and MAPKs before exposure to AngII or Ang-(1-7). The human fetal lung-1 cells were infected with lentivirus-mediated ACE2 before exposure to AngII. In vivo, Ang-(1-7) prevented BLM-induced lung fibrosis and AngII-induced lung inflammation by inhibiting the MAPK phosphorylation and NF-κB signaling cascades. However, exogenous Ang-(1-7) alone clearly promoted lung inflammation. In vitro, Ang-(1-7) and lentivirus-mediated ACE2 inhibited the AngII-induced MAPK/NF-κB pathway, thereby attenuating inflammation and α-collagen I production, which could be reversed by the Mas inhibitor, A-779. Ang-(1-7) inhibited AngII-induced lung fibroblast apoptotic resistance via inhibition of the MAPK/NF-κB pathway and activation of the BCL-2-associated X protein/caspase-dependent mitochondrial apoptotic pathway. Ang-(1-7) alone markedly stimulated extracellular signal-regulated protein kinase 1/2 phosphorylation and the NF-κB cascade. Up-regulation of the ACE2/Ang-(1-7)/Mas axis protected against pulmonary fibrosis by inhibiting the MAPK/NF-κB pathway. However, close attention should be paid to the proinflammatory effects of Ang-(1-7).

Authors+Show Affiliations

1 Department of Respiratory Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24168260

Citation

Meng, Ying, et al. "Angiotensin-converting Enzyme 2/angiotensin-(1-7)/Mas Axis Protects Against Lung Fibrosis By Inhibiting the MAPK/NF-κB Pathway." American Journal of Respiratory Cell and Molecular Biology, vol. 50, no. 4, 2014, pp. 723-36.
Meng Y, Yu CH, Li W, et al. Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway. Am J Respir Cell Mol Biol. 2014;50(4):723-36.
Meng, Y., Yu, C. H., Li, W., Li, T., Luo, W., Huang, S., Wu, P. S., Cai, S. X., & Li, X. (2014). Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway. American Journal of Respiratory Cell and Molecular Biology, 50(4), 723-36. https://doi.org/10.1165/rcmb.2012-0451OC
Meng Y, et al. Angiotensin-converting Enzyme 2/angiotensin-(1-7)/Mas Axis Protects Against Lung Fibrosis By Inhibiting the MAPK/NF-κB Pathway. Am J Respir Cell Mol Biol. 2014;50(4):723-36. PubMed PMID: 24168260.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis protects against lung fibrosis by inhibiting the MAPK/NF-κB pathway. AU - Meng,Ying, AU - Yu,Chang-Hui, AU - Li,Wei, AU - Li,Ting, AU - Luo,Wei, AU - Huang,Shan, AU - Wu,Ping-Sheng, AU - Cai,Shao-Xi, AU - Li,Xu, PY - 2013/10/31/entrez PY - 2013/10/31/pubmed PY - 2014/6/18/medline SP - 723 EP - 36 JF - American journal of respiratory cell and molecular biology JO - Am J Respir Cell Mol Biol VL - 50 IS - 4 N2 - Accumulating evidence has demonstrated that up-regulation of the angiotensin (Ang)-converting enzyme (ACE)/AngII/AngII type 1 receptor (AT1R) axis aggravates pulmonary fibrosis. The recently discovered ACE2/Ang-(1-7)/Mas axis, which counteracts the activity of the ACE/AngII/AT1R axis, has been shown to protect against pulmonary fibrosis. However, the mechanisms by which ACE2 and Ang-(1-7) attenuate pulmonary fibrosis remain unclear. We hypothesized that up-regulation of the ACE2/Ang-(1-7)/Mas axis protects against bleomycin (BLM)-induced pulmonary fibrosis by inhibiting the mitogen-activated protein kinase (MAPK)/NF-κB pathway. In vivo, Ang-(1-7) was continuously infused into Wistar rats that had received BLM or AngII. In vitro, human fetal lung-1 cells were pretreated with compounds that block the activities of AT1R, Mas (A-779), and MAPKs before exposure to AngII or Ang-(1-7). The human fetal lung-1 cells were infected with lentivirus-mediated ACE2 before exposure to AngII. In vivo, Ang-(1-7) prevented BLM-induced lung fibrosis and AngII-induced lung inflammation by inhibiting the MAPK phosphorylation and NF-κB signaling cascades. However, exogenous Ang-(1-7) alone clearly promoted lung inflammation. In vitro, Ang-(1-7) and lentivirus-mediated ACE2 inhibited the AngII-induced MAPK/NF-κB pathway, thereby attenuating inflammation and α-collagen I production, which could be reversed by the Mas inhibitor, A-779. Ang-(1-7) inhibited AngII-induced lung fibroblast apoptotic resistance via inhibition of the MAPK/NF-κB pathway and activation of the BCL-2-associated X protein/caspase-dependent mitochondrial apoptotic pathway. Ang-(1-7) alone markedly stimulated extracellular signal-regulated protein kinase 1/2 phosphorylation and the NF-κB cascade. Up-regulation of the ACE2/Ang-(1-7)/Mas axis protected against pulmonary fibrosis by inhibiting the MAPK/NF-κB pathway. However, close attention should be paid to the proinflammatory effects of Ang-(1-7). SN - 1535-4989 UR - https://www.unboundmedicine.com/medline/citation/24168260/Angiotensin_converting_enzyme_2/angiotensin__1_7_/Mas_axis_protects_against_lung_fibrosis_by_inhibiting_the_MAPK/NF_κB_pathway_ L2 - https://www.atsjournals.org/doi/10.1165/rcmb.2012-0451OC?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -