Galectin-3 levels are elevated following nintedanib treatment
Gali Epstein Shochet1, Alon Pomerantz2, David Shitrit3
1Pulmonary Department, Meir Medical Center, 59 Tchernichovsky Street, Kfar Saba 4428164, Israel.
Therapeutic Advances in Chronic Disease
|March 12, 2021
Summary
Nintedanib increases Galectin-3 (Gal-3) levels in experimental models and IPF patients. This suggests potential for combined therapies targeting Gal-3 in idiopathic pulmonary fibrosis (IPF).
Area of Science:
- Pulmonology
- Fibrosis Research
- Pharmacology
Background:
- Idiopathic pulmonary fibrosis (IPF) is a severe lung disease.
- Nintedanib is an approved IPF treatment.
- Galectin-3 (Gal-3) is a profibrotic factor; its inhibitor TD139 is in trials.
Purpose of the Study:
- To evaluate nintedanib's effect on Gal-3 expression.
- To inform potential combination therapy with Gal-3 inhibitors.
Main Methods:
- Assessed Gal-3 in lung tissue, primary human lung fibroblasts (HLFs), and a mouse fibrosis model.
- Quantified Gal-3 mRNA and protein levels.
- Analyzed serum Gal-3 in IPF patients with/without nintedanib treatment.
Main Results:
- Nintedanib increased Gal-3, pSTAT3, and IL-8 mRNA in HLFs.
- IPF tissues showed higher Gal-3 than controls.
- Nintedanib further elevated Gal-3 in a mouse fibrosis model, particularly in macrophages.
- Patients on nintedanib had higher serum Gal-3 levels.
Conclusions:
- Nintedanib significantly elevates Gal-3 levels in vitro, in vivo, and in patients.
- Findings support exploring combination therapy for IPF using nintedanib and Gal-3 inhibitors.
