Related Experiment Video
Updated: Feb 22, 2026
Refined Murine Model of Idiopathic Pulmonary Fibrosis
Published on: June 17, 2025
Beneficial effects of bile acid receptor agonists in pulmonary disease models
Paolo Comeglio1, Annamaria Morelli2, Luciano Adorini3
1a Department of Biomedical, Experimental and Clinical Sciences , University of Florence , Florence , Italy.
Introduction:
Bile acids act as steroid hormones, controlling lipid, glucose and energy metabolism, as well as inflammation and fibrosis. Their actions are implemented through activation of nuclear (FXR, VDR, PXR) and membrane G protein-coupled (TGR5, S1PR2) receptors. Areas covered: This review discusses the potential of FXR and TGR5 as therapeutic targets in the treatment of pulmonary disorders linked to metabolism and/or inflammation. Obeticholic acid (OCA) is the most clinically advanced bile acid-derived agonist for FXR-mediated anti-inflammatory and anti-fibrotic effects. It therefore represents an attractive pharmacological approach for the treatment of lung conditions characterized by vascular and endothelial dysfunctions. Expert opinion: Inflammation, vascular remodeling and fibrotic processes characterize the progression of pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF). These processes are only partially targeted by the available therapeutic options and still represent a relevant medical need. The results hereby summarized demonstrate OCA efficacy in preventing experimental lung disorders, i.e. monocrotaline-induced PAH and bleomycin-induced fibrosis, by abating proinflammatory and vascular remodeling progression. TGR5 is also expressed in the lung, and targeting the TGR5 pathway, using the TGR5 agonist INT-777 or the dual FXR/TGR5 agonist INT-767, could also contribute to the treatment of pulmonary disorders mediated by inflammation and fibrosis.
Insights
Bile acids, like Obeticholic acid (OCA), show promise in treating lung diseases by targeting inflammation and fibrosis. Activating FXR and TGR5 receptors may offer new therapies for pulmonary arterial hypertension and idiopathic pulmonary fibrosis.
Area of Science:
- Metabolic regulation and steroid hormone action.
- Pulmonary medicine and pharmacology.
Background:
- Bile acids function as steroid hormones regulating metabolism, inflammation, and fibrosis.
- They exert effects via nuclear (FXR, VDR, PXR) and membrane (TGR5, S1PR2) receptors.
Purpose of the Study:
- To review the therapeutic potential of FXR and TGR5 as targets for pulmonary disorders.
- To evaluate Obeticholic acid (OCA) as a FXR agonist for lung conditions.
Main Methods:
- Review of literature on bile acid receptors and pulmonary diseases.
- Discussion of experimental models for pulmonary arterial hypertension (PAH) and idiopathic pulmonary fibrosis (IPF).
Main Results:
- Obeticholic acid (OCA) demonstrates efficacy in preventing experimental PAH and lung fibrosis.
- OCA reduces inflammation and vascular remodeling in lung disease models.
- TGR5 agonists (INT-777) and dual FXR/TGR5 agonists (INT-767) show potential for treating inflammatory and fibrotic lung disorders.
Conclusions:
- FXR and TGR5 represent promising therapeutic targets for pulmonary diseases.
- OCA offers a potential treatment strategy for lung conditions involving inflammation and fibrosis.
- Targeting bile acid pathways could address unmet medical needs in PAH and IPF.
Related Concept Videos
01:25Antiasthma Drugs: β2-Adrenoceptor Agonists
One class of bronchodilators includes β2-adrenoceptor agonists. These agents target the β2-adrenoceptors located on bronchial smooth muscle cells. By stimulating these receptors, β2-agonists induce...
01:17Drugs Used in Lower Respiratory Disorders: Overview
Bronchodilators, the first step of respiration enhancement, come in various forms, each with its own mechanism...
01:19Antiasthma Drugs: Leukotriene Modifiers
Leukotriene modifiers work through two distinct mechanisms:
01:23Treatment for Pulmonary Arterial Hypertension: Prostacyclin Receptor Agonists
These agonists bind to the IPR receptor situated on the plasma membrane of the pulmonary artery smooth muscle cells. This binding triggers a cascade of reactions known as the GS-AC-cAMP-PKA pathway. This pathway results in the relaxation of smooth muscle...
01:11Direct-Acting Cholinergic Agonists: Therapeutic Uses
01:20Antiasthma Drugs: Muscarinic Receptor Antagonists
Antimuscarinic agents compete with ACh for the same binding site on the muscarinic receptors. By binding to these receptors, they inhibit the downstream effects of ACh and block the parasympathetic...