Combination of HSP90 Inhibitors and HSP70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis in Rabbits

Authors

Ruben M. L. Colunga Biancatelli, Old Dominion UniversityFollow
Pavel A. Solopov, Old Dominion UniversityFollow
Tierney Day, Old Dominion UniversityFollow
Dan E. Austin Jr., Macon & Joan Brock Virginia Health Sciences at Old Dominion UniversityFollow
Len E. Murray, Old Dominion UniversityFollow
John D. Catravas, Old Dominion UniversityFollow

Document Type

Article

Publication Date

2025

Publication Title

International Journal of Molecular Sciences

Volume

26

Issue

2

Pages

441 (1-13)

DOI

10.3390/ijms26020441

Abstract

Combined therapies with Heat Shock Protein 90 (HSP90) inhibitors and Heat Shock Protein 70 (HSP70) inducers are gaining significant interest in cancer and cardiovascular research. Here, we tested the hypothesis that HSP90 inhibitors and HSP70 inducers, together, can block the development of pulmonary fibrosis. We exposed New Zealand White Rabbits to hydrochloric acid (HCl, 0.1 N, 1.5 mL/kg), one of the top five chemicals most commonly involved in accidental exposures and inhalation injuries worldwide, and treated animals with either the orally available HSP90 inhibitor TAS-116 (1.7 mg/kg 5x/week) or TAS-116 combined with the HSP70 inducer, geranylgeranyl acetone (GGA, 50 mg/kg, 3x/week). At 60 days post-HCl instillation, TAS and GGA treatment markedly reduced the degree of pulmonary fibrosis, lung dysfunction, and activation of profibrotic pathways. The use of HSP70 inducers may be a helpful tool to improve the profile of HSP90 inhibitors and reduce their minimal effective dose and side effects. Further investigation is required to explore the exact synergistic mechanism behind the antifibrotic profile of HSP90 inhibitors and HSP70 inducers.

Rights

© 2025 The Authors.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International (CC BY 4.0) License.

Data Availability

Article states: "Data can be made available by the authors upon reasonable request."

Original Publication Citation

Colunga Biancatelli, R. M. L., Solopov, P. A., Day, T., Austin, D. E., Murray, L. E., & Catravas, J. D. (2025). Combination of HSP90 inhibitors and HSP70 inducers prevent hydrochloric acid-induced pulmonary fibrosis in rabbits. International Journal of Molecular Sciences, 26(2), 1-13, Article 441. https://doi.org/10.3390/ijms26020441

Repository Citation

Colunga Biancatelli, Ruben M. L.; Solopov, Pavel A.; Day, Tierney; Austin, Dan E. Jr.; Murray, Len E.; and Catravas, John D., "Combination of HSP90 Inhibitors and HSP70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis in Rabbits" (2025). Bioelectrics Publications. 377.
https://digitalcommons.odu.edu/bioelectrics_pubs/377

ORCID

0000-0002-1174-3876 (Colunga Biancatelli), 0000-0002-1705-027X (Solopov), 0000-0002-5098-295X (Catravas)