Actividad Investigadora
Endomask19: Desarrollo de mascarilla endoscópica de protección frente a gotas y aerosoles expulsados en procedimientos con pacientes COVID
Datos básicos
- Código:
- INNVAL20/21
- Dotación:
- 25.000,00 €
- Año Inicial:
- 2020
- Año final:
- 2023
Objetivos del proyecto
Summary: COVID-19 patients with pneumonia may develop extensive pulmonary fibrosis, which compromise lung function, thus the patient survival. This project pursues the reduction of COVID-19 associated pulmonary fibrosis with antifibrotic compounds that regulate lung fibroblasts and potentiate SARS-CoV2-infected alveolar cell regeneration which exercise a positive feedback. More specifically, we will apply an antifibrotic therapy that already succeeded in fibroblasts from other organs, reinforce it with pro-telomeric natural compounds to protect the alveolar cells and study the role of telomeres length changes in the origin and protection from the disease. Hsp90 inhibitors: The most severe consequences of SARS-CoV2 infection is the pneumonia in most cases associated to pulmonary fibrosis, opening a communication between the infected epithelial cells and the fibroblasts (4). It is largely studied the fibrosis reduction through strategies related to the main profibrotic cytokine Transforming Growth Factor (TGFß)(17). TGFß also participates in the activation of dysfunctional telomeric actions (26) and the deregulation of its profibrotic cascade allows the protection of long telomeres and cell regeneration. Heat shock Protein 90 (Hsp90) chaperone potentiates TGFß cascade (1) and some of its inhibitors reduces TGFß-mediated fibrosis preserving the cell homeostasis (2). (Objective 1) We will work with a co-culture of SARSCoV2 infected-human alveolar cell type II (ATII) and human lung fibroblasts. We will check collagen production before and after the anti-fibrotic treatment with commercial and preclinical tested Hsp90 inhibitors that include homeostatic preservative actions previously proved in our group (2). Telomeres shortening: Age or stress promotes repetitive cell division which shorten the cell telomeres. When cell telomeres are too short the tissue regeneration capability diminishes, and age-related diseases are prone to appear (24). The origin of pulmonary fibrosis from different etiologies (including COVID-19 associated) are related to a lack of the pulmonary type II alveolar cells (ATII) regeneration (5). Telomeres shortening in ATII cells caused by the SARS-CoV2 infection could be behind the rapid disease progression. An antifibrotic therapy which includes protection of telomere shortening would lead to an effective treatment for COVID-19 associated pulmonary fibrosis. (Objective 2) This project will study (with the collaboration of one of the biggest experts in telomeres dysfunction) if the lung fibrosis contention and the telomere length are related events. Plant derivatives: The vegetal stem cells produce and secrete natural compounds that retain telomere length. A consolidated expert in agriculture genomics and collaborator of this project will proceed for (Objective 3) a screening of molecules from cell culture of plants with pro-telomeric protection capabilities to reinforce the antifibrotic treatment. Those plant derivates together with Hsp90 inhibitors will potentiate cell regeneration of ATII, protect cell homeostasis and enhance the antifibrotic action. The strategic interest for the institution: Under this clear perspective of treating COVID-19 associated pulmonary fibrosis and understanding the relation with telomeres shortening; the strategic interest for the institution is the obtention of new drugs in preclinical phase: -to promote ATII cell regeneration reducing the telomeric dysfunction and - to control the profibrotic cascade of uncontrolled fibroblasts. This combination will reconduct the lung to a healthy state. We foster scientific alliances to carry out translational research to have an international impact on the clinical activity related to COVID-19.
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