Inflammatory Injury Caused by Silica Exposure

接触二氧化硅引起的炎症损伤

基本信息

批准号：
10657137
负责人：
Jian Fu
金额：
$ 38.25万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-01 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10657137
关键词：
AKT1 gene Acetylation Alveolar Macrophages Alveolus Autoimmune Diseases Binding Cell physiology Chronic Clinical Trials Cytoplasm Deacetylase Deacetylation Deposition Diagnosis Disease Dust Exposure to Fibrosis Functional disorder Future Genetic Transcription HDAC6 gene Inflammation Inflammatory Inflammatory Response Ingestion Inhalation Injury Leukocytes Malignant Neoplasms Mediating Mediator Microtubule Stabilization Microtubules Molecular Myelogenous Nuclear Translocation Pathogenesis Patients Persons Phenotype Phosphorylation Play Production Profibrotic signal Pulmonary Fibrosis Pulmonary Inflammation Regulation Reporting Risk Role Signal Transduction Silicon Dioxide Silicosis TNF gene Testing Therapeutic Transforming Growth Factor beta Tubulin Work alpha Tubulin effective therapy mouse model novel particle protective effect protein function response therapeutic target transcriptomics

项目摘要

Project Summary More than 2 million people in the US are exposed to respirable crystalline silica at work. Inhalation of dust containing respirable crystalline silica causes silicosis, which is characterized by chronic inflammation and pulmonary fibrosis. Silica exposure also increases the risk of developing autoimmune diseases and cancer. Silicosis patients have a median survival of 6 years after diagnosis. The pathophysiology of silicosis has not been fully understood. Currently, there is no effective treatment against this devastating disease. It has been reported that the dysregulation of alveolar macrophages plays an important role in the pathogenesis of silicosis. The deposition of fine silica particles in alveoli and the ingestion of silica particles by alveolar macrophages trigger pro-inflammatory and pro-fibrotic responses. However, molecular mechanisms of the dysregulated alveolar macrophage responses remain elusive. Using a mouse model of silicosis, our preliminary studies indicate that myeloid HDAC6 plays an essential role in the pathogenesis of silicosis. In the proposed studies, we will test the hypothesis that myeloid HDAC6 is a key mediator of pro-inflammatory and pro-fibrotic responses in silicosis. We will investigate the specific role of myeloid HDAC6 in silicosis and evaluate the therapeutic potential of HDAC6 as a target to treat silicosis.

项目摘要美国有超过200万人在工作中暴露于可呼吸的结晶二氧化硅。吸入含有可呼吸的晶体二氧化硅的灰尘会引起硅化作用，其特征是慢性炎症和肺纤维化。二氧化硅暴露还增加了发展的风险自身免疫性疾病和癌症。硅化病患者的中位生存期在6年后诊断。硅质病的病理生理尚未完全了解。目前，没有有效治疗这种毁灭性疾病。据报道，失调肺泡巨噬细胞的作用在硅化病的发病机理中起重要作用。沉积肺泡中的细二氧化硅颗粒和肺泡巨噬细胞摄入二氧化硅颗粒促炎和促纤维化反应。但是，分子机制肺泡巨噬细胞反应失调仍然难以捉摸。使用小鼠硅化模型，我们的初步研究表明，髓样HDAC6在发病机理中起着至关重要的作用硅化作用。在拟议的研究中，我们将检验以下假设：髓样HDAC6是关键硅化作用中促炎和纤维化反应的介体。我们将调查髓样HDAC6在硅化中的具体作用，并评估HDAC6的治疗潜力治疗硅氧症的靶标。