Dataset Information

Galectin-3 levels are elevated following nintedanib treatment.

ABSTRACT:

Background and aims

Idiopathic pulmonary fibrosis (IPF) is a common and severe form of pulmonary fibrosis. Nintedanib, a triple angiokinase inhibitor, is approved for treating IPF. Galectin 3 (Gal-3) activates a variety of profibrotic processes. Currently, the Gal-3 inhibitor TD139 is being tested in phase II clinical trials. Since this treatment is given 'on top' of nintedanib, it is important to estimate its effect on Gal-3 levels. Therefore, we evaluated the impact of nintedanib on Gal-3 expression using both in vitro and in vivo models, in addition to serum samples from patients with IPF.

Methods

Gal-3 levels were evaluated in IPF and control tissue samples, primary human lung fibroblasts (HLFs) following nintedanib treatment (10-100 nM, quantitative polymerase chain reaction), and in a silica-induced fibrosis mouse model with/without nintedanib (0.021-0.21 mg/kg) by immunohistochemistry. In addition, Gal-3 levels were analyzed in serum samples from 41 patients with interstitial lung disease patients with/without nintedanib treatment by ELISA.

Results

Nintedanib addition to HLFs resulted in significant elevations in Gal-3, phospho-signal transducer and activator of transcription 3 (pSTAT3), as well as IL-8 mRNA levels (p < 0.05). Gal-3 expression was higher in samples from IPF patients compared with non-IPF controls at the protein and mRNA levels (p < 0.05). In the in vivo mouse model, Gal-3 levels were increased following fibrosis induction and even further increased with the addition of nintedanib, mostly in macrophages (p < 0.05). Patients receiving nintedanib presented with higher Gal-3 serum levels compared with those who did not receive nintedanib (p < 0.05).

Conclusion

Nintedanib elevates Gal-3 levels in both experimental models, along with patient samples. These findings highlight the possibility of using combined inhibition therapy for patients with IPF.

SUBMITTER: Shochet GE

PROVIDER: S-EPMC7907712 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Galectin-3 levels are elevated following nintedanib treatment.

Shochet Gali Epstein GE Pomerantz Alon A Shitrit David D Bardenstein-Wald Becky B Ask Kjetil K Surber Mark M Rabinowicz Noa N Levy Yair Y Benchetrit Sydney S Edelstein Evgeny E Zitman-Gal Tali T

Therapeutic advances in chronic disease 20201127

<h4>Background and aims</h4>Idiopathic pulmonary fibrosis (IPF) is a common and severe form of pulmonary fibrosis. Nintedanib, a triple angiokinase inhibitor, is approved for treating IPF. Galectin 3 (Gal-3) activates a variety of profibrotic processes. Currently, the Gal-3 inhibitor TD139 is being tested in phase II clinical trials. Since this treatment is given 'on top' of nintedanib, it is important to estimate its effect on Gal-3 levels. Therefore, we evaluated the impact of nintedanib on Ga ...[more]

PMID: 33708368

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Dataset Information

Galectin-3 levels are elevated following nintedanib treatment.

Background and aims

Methods

Results

Conclusion

Publications

Galectin-3 levels are elevated following nintedanib treatment.

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