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Full-Text Articles in Respiratory Tract Diseases

Combination Of Hsp90 Inhibitors And Hsp70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis In Rabbits, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Dan E. Austin Jr., Len E. Murray, John D. Catravas Jan 2025

Combination Of Hsp90 Inhibitors And Hsp70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis In Rabbits, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Dan E. Austin Jr., Len E. Murray, John D. Catravas

Bioelectrics Publications

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, …


Optimizing Antidotal Treatment With The Oral Hsp90 Inhibitor Tas-116 Against Hydrochloric Acid-Induced Pulmonary Fibrosis In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropolou, Tierney Day, John Catravas Jan 2022

Optimizing Antidotal Treatment With The Oral Hsp90 Inhibitor Tas-116 Against Hydrochloric Acid-Induced Pulmonary Fibrosis In Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropolou, Tierney Day, John Catravas

Bioelectrics Publications

Exposure to high concentrations of hydrochloric acid (HCl) can lead to severe acute and chronic lung injury. In the aftermath of accidental spills, victims may be treated for the acute symptoms, but the chronic injury is often overlooked. We have developed a mouse model of acute and chronic lung injury, in which the peak of acute lung injury occurs on the day 4 after HCl exposure. We have also demonstrated that HSP90 inhibitors are effective antidotes when administered starting 24 h after HCl. In this study we examined the hypothesis that the novel oral HSP90 inhibitor TAS-116 can effectively ameliorate …


Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression And Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1–Induced Acute Lung Injury In K18-Hace2 Transgenic Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, John D. Catravas Jan 2022

Alcohol Increases Lung Angiotensin-Converting Enzyme 2 Expression And Exacerbates Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein Subunit 1–Induced Acute Lung Injury In K18-Hace2 Transgenic Mice, Pavel A. Solopov, Ruben Manuel Luciano Colunga Biancatelli, John D. Catravas

Bioelectrics Publications

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, alcohol consumption increased markedly. Nearly one in four adults reported drinking more alcohol to cope with stress. Chronic alcohol abuse is now recognized as a factor complicating the course of acute respiratory distress syndrome. and increasing mortality. To investigate the mechanisms behind this interaction, we developed a combined acute respiratory distress syndrome and chronic alcohol abuse mouse model by intratracheally instilling the S1 subunit of SARS-CoV-2 spike protein (S1SP) in K18-human angiotensin-converting enzyme 2 (ACE2) transgenic mice that express the human ACE2 receptor for SARS-CoV-2 and are kept on an …


The Heat Shock Protein 90 Inhibitor, At13387, Protects The Alveolo-Capillary Barrier And Prevents Hci-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, Betsy Gregory, Tierney Day, John D. Catravas Jan 2022

The Heat Shock Protein 90 Inhibitor, At13387, Protects The Alveolo-Capillary Barrier And Prevents Hci-Induced Chronic Lung Injury And Pulmonary Fibrosis, Ruben M.L. Colunga Biancatelli, Pavel Solopov, Christiana Dimitropoulou, Betsy Gregory, Tierney Day, John D. Catravas

Bioelectrics Publications

Hydrochloric acid (HCl) exposure causes asthma-like conditions, reactive airways dysfunction syndrome, and pulmonary fibrosis. Heat Shock Protein 90 (HSP90) is a molecular chaperone that regulates multiple cellular processes. HSP90 inhibitors are undergoing clinical trials for cancer and are also being studied in various pre-clinical settings for their anti-inflammatory and anti-fibrotic effects. Here we investigated the ability of the heat shock protein 90 (HSP90) inhibitor AT13387 to prevent chronic lung injury induced by exposure to HCl in vivo and its protective role in the endothelial barrier in vitro. We instilled C57Bl/6J mice with 0.1N HCl (2 µL/g body weight, intratracheally) and …


Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury And Pulmonary Fibrosis In Mice, Pavel Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropoulou, John D. Catravas Jan 2021

Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury And Pulmonary Fibrosis In Mice, Pavel Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as …


Sex-Related Differences In Murine Models Of Chemically Induced Pulmonary Fibrosis, Pavel Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropoulou, John D. Catravas Jan 2021

Sex-Related Differences In Murine Models Of Chemically Induced Pulmonary Fibrosis, Pavel Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

We developed two models of chemically induced chronic lung injury and pulmonary fibrosis in mice (intratracheally administered hydrochloric acid (HCl) and intratracheally administered nitrogen mustard (NM)) and investigated male-female differences. Female mice exhibited higher 30-day survival and less weight loss than male mice. Thirty days after the instillation of either HCl or NM, bronchoalveolar lavage fluid displayed a persistent, mild inflammatory response, but with higher white blood cell numbers and total protein content in males vs. females. Furthermore, females exhibited less collagen deposition, milder pulmonary fibrosis, and lower Ashcroft scores. After instillation of either HCl or NM, all animals displayed …


Hsp90 Inhibitors For Ipf/Covid-19, Ruben Manuel Luciano Colunga Biancatelli, Pavel A. Solopov, John Catravas Jan 2020

Hsp90 Inhibitors For Ipf/Covid-19, Ruben Manuel Luciano Colunga Biancatelli, Pavel A. Solopov, John Catravas

Bioelectrics Publications

Heat shock protein 90 (HSP90) is an important chaperone that assists the late stage folding of several proteins involved in cell survival in response to environmental stressors. The inhibition of HSP90 is followed by a complex modulation of the proteome and the kinome, that has proved beneficial in cancer and various neurodegenerative diseases. Additionally, accumulating literature suggests that HSP90 may be a key target during the development of pulmonary fibrosis and that its inhibition could serve as a new and exciting therapeutic approach. We have summarized the current evidence about HSP90’s role in Idiopathic Pulmonary Fibrosis (IPF), the results from …


Hsp90 Inhibition And Modulation Of The Proteome: Therapeutical Implications For Idiopathic Pulmonary Fibrosis (Ipf), Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy Gregory, John D. Catravas Jan 2020

Hsp90 Inhibition And Modulation Of The Proteome: Therapeutical Implications For Idiopathic Pulmonary Fibrosis (Ipf), Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy Gregory, John D. Catravas

Bioelectrics Publications

Idiopathic Pulmonary fibrosis (IPF) is a catastrophic disease with poor outcomes and limited pharmacological approaches. Heat shock protein 90 (HSP90) has been recently involved in the wound-healing pathological response that leads to collagen deposition in patients with IPF and its inhibition represents an exciting drug target against the development of pulmonary fibrosis. Under physiological conditions, HSP90 guarantees proteostasis through the refolding of damaged proteins and the degradation of irreversibly damaged ones. Additionally, its inhibition, by specific HSP90 inhibitors (e.g., 17 AAG, 17 DAG, and AUY-922) has proven beneficial in different preclinical models of human disease. HSP90 inhibition modulates a complex …