# The role of the classical renin–angiotensin system and angiotensin-converting enzyme 2/Ang(1–7)/Mas axis in pulmonary fibrosis

## TL;DR

This paper reviews how the renin–angiotensin system, including ACE2 and Ang(1–7), influences the development and progression of pulmonary fibrosis.

## Contribution

The paper provides an updated overview of both classical and non-classical RAS pathways in pulmonary fibrosis.

## Key findings

- Ang II promotes fibrosis through AT1R but has contrasting effects through AT2R.
- ACE2 converts Ang II into Ang(1–7), which exerts anti-fibrotic effects via the Mas receptor.
- RAS influences autophagy, oxidative stress, and inflammation in pulmonary fibrosis progression.

## Abstract

Pulmonary fibrosis (PF), a progressive and fatal disease, is characterized by fibroblast proliferation, excessive extracellular matrix deposition, and collagen synthesis. These pathological changes lead to impaired lung structure and function, ultimately resulting in respiratory failure. Emerging basic and clinical evidence highlight the renin–angiotensin system (RAS) as a critical contributor to PF onset and progression. Angiotensin (Ang) II, a key RAS component, mediates various biological effects through its receptors, Ang II receptor type 1 (AT1R) and Ang II receptor type 2 (AT2R). Ang II promotes vasoconstriction, inflammation, and fibrosis via AT1R, while it shows contrasting effects through AT2R. Angiotensin-converting enzyme 2 (ACE2) plays a significant role in RAS by converting Ang II into Ang (1–7), which in turn interacts with Mas receptor and Mas-associated G-protein-coupled receptor D to exert anti-inflammatory, anti-apoptotic, and anti-fibrotic effects. The RAS also influences autophagy, oxidative stress, and inflammation in the progression of PF. This review provides an updated overview of the roles of the classical and non-classical RAS pathways in PF.