ArticleAntioxidants & redox signaling2015
The angiotensin-converting enzyme 2/angiotensin (1-7)/Mas axis protects against lung fibroblast migration and lung fibrosis by inhibiting the NOX4-derived ROS-mediated RhoA/Rho kinase pathway.
Article in Antioxidants & redox signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04331470 (Evaluation of Efficacy of Pharmacotherapy Treatment of COVID- 19 Infection Using Oral Levamisole and Formoterol+Budesonide Inhaler and Comparison of This Treatment Protocol With Standard National Treatment of the Disease), which is not on this map. Cited by 86 papers.
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Evaluation of Efficacy of Pharmacotherapy Treatment of COVID- 19 Infection Using Oral Levamisole and Formoterol+Budesonide Inhaler and Comparison of This Treatment Protocol With Standard National Treatment of the Disease
Who cites it
86 citing papers in PubMed, 153 citations in OpenAlex.
- Imbalance of renin-angiotensin system in calcium oxalate crystals-induced renal oxidative stress and autophagy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Bronchopulmonary dysplasia induced by hyperoxia attenuated by A GLP-1 analog, Liraglutide, by regulating the ACE-2/Ang(1-7)/Mas receptor pathway.Pediatric research · 2026Article
- The Mechanism of Oxidative Stress in Pulmonary Fibrosis and Research Progress.Antioxidants (Basel, Switzerland) · 2026Review
- Angiotensin-(1-7) in asthma and pulmonary fibrosis: mechanisms of action, clinical safety, and nano-delivery strategies.Frontiers in pharmacology · 2026Review
- Micheliolide attenuates sepsis-induced acute lung injury by suppressing mitochondrial oxidative stress and PFKFB3-driven glycolysis.Journal of translational medicine · 2025Article
- The role of the classical renin-angiotensin system and angiotensin-converting enzyme 2/Ang(1-7)/Mas axis in pulmonary fibrosis.Frontiers in medicine · 2025Review
- Revisiting pulmonary fibrosis: inflammatory dynamics of the lipofibroblast-to-inflammatory lipofibroblast-to-activated myofibroblast reversible switch.Frontiers in immunology · 2025Review
- Pulmonary inflammation and viral replication define distinct clinical outcomes in fatal cases of COVID-19.PLoS pathogens · 2024Article
- MicroRNA‑200c‑3p regulates seawater‑induced acute lung injury via ANGII and ACE2/ANG1‑7 pathways.Experimental and therapeutic medicine · 2023Article
- The RAAS Goodfellas in Cardiovascular System.Journal of clinical medicine · 2023Review
- Mas receptor: a potential strategy in the management of ischemic cardiovascular diseases.Cell cycle (Georgetown, Tex.) · 2023Review
- KRIT1: A Traffic Warden at the Busy Crossroads Between Redox Signaling and the Pathogenesis of Cerebral Cavernous Malformation Disease.Antioxidants & redox signaling · 2023Review
- Alamandine/MrgD axis prevents TGF-β1-mediated fibroblast activation via regulation of aerobic glycolysis and mitophagy.Journal of translational medicine · 2023Article
- Qing Fei Hua Xian Decoction ameliorates bleomycin-induced pulmonary fibrosis by suppressing oxidative stress through balancing ACE-AngII-AT1R/ACE2-Ang-(1-7)-Mas axis.Iranian journal of basic medical sciences · 2023Article
- Effects of Smoking on COVID-19 Management and Mortality: An Umbrella Review.Journal of smoking cessation · 2023Review
- Ageing of skeletal muscle extracellular matrix and mitochondria: finding a potential link.Annals of medicine · 2023Review
- The Role of Tβ4-POP-Ac-SDKP Axis in Organ Fibrosis.International journal of molecular sciences · 2022Review
- Pharmacological Treatment for Neuroinflammation in Stress-Related Disorder.Biomedicines · 2022Review
- Metal-based complexes against SARS-CoV-2.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2022Review
- Development of Metal Complexes for Treatment of Coronaviruses.International journal of molecular sciences · 2022Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledReactive oxygen species (ROS) generated by NADPH oxidase-4 (NOX4) have been shown to initiate lung fibrosis. The migration of lung fibroblasts to the injured area is a crucial early step in lung fibrosis. The angiotensin-converting enzyme 2 (ACE2)/angiotensin (1-7) [Ang(1-7)]/Mas axis, which counteracts the ACE/angiotensin II (AngII)/angiotensin II type 1 receptor (AT1R) axis, has been shown to attenuate pulmonary fibrosis. Nevertheless, the exact molecular mechanism remains unclear.
aimsTo investigate the different effects of the two axes of the renin-angiotensin system (RAS) on lung fibroblast migration and extracellular matrix accumulation by regulating the NOX4-derived ROS-mediated RhoA/Rho kinase (Rock) pathway.
resultsIn vitro, AngII significantly increased the NOX4 level and ROS production in lung fibroblasts, which stimulated cell migration and α-collagen I synthesis through the RhoA/Rock pathway. These effects were attenuated by N-acetylcysteine (NAC), diphenylene iodonium, and NOX4 RNA interference. Moreover, Ang(1-7) and lentivirus-mediated ACE2 (lentiACE2) suppressed AngII-induced migration and α-collagen I synthesis by inhibiting the NOX4-derived ROS-mediated RhoA/Rock pathway. However, Ang(1-7) alone exerted analogous effects on AngII. In vivo, constant infusion with Ang(1-7) or intratracheal instillation with lenti-ACE2 shifted the RAS balance toward the ACE2/Ang(1-7)/Mas axis, alleviated bleomycin-induced lung fibrosis, and inhibited the RhoA/Rock pathway by reducing NOX4-derived ROS. INNOVATION: This study suggests that the ACE2/Ang(1-7)/Mas axis may be targeted by novel pharmacological antioxidant strategies to treat lung fibrosis induced by AngII-mediated ROS.
conclusionThe ACE2/Ang(1-7)/Mas axis protects against lung fibroblast migration and lung fibrosis by inhibiting the NOX4-derived ROS-mediated RhoA/Rock pathway.
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