Homoharringtonine exerts anti-silicosis effects by inhibiting the CCR1 and PI3K/AKT signaling pathways in lung fibroblasts
Xinying Jia1
Ziwei Li1
Xiyue Hu2
Ting Wang3
Wenxiu Lian1
Wenqing Sun4
Yi Liu1
Chunhui Ni5
1.Department of Occupational Medicine and Environmental Health,Key Laboratory of Modern Toxicology of Ministry of Education,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China2.Department of Public Health,Kangda College of Nanjing Medical University,Lianyungang,Jiangsu 222000,China;Community Health Service Center of Anzhen Street,Xishan District,Wuxi,Jiangsu 214035,China3.Department of Occupational Medicine and Environmental Health,Key Laboratory of Modern Toxicology of Ministry of Education,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Pathology,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing,Jiangsu 210000,China4.The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University,Wuxi Center for Disease Control and Prevention,Wuxi Medical Center,Nanjing Medical University,Wuxi,Jiangsu 214400,China5.Department of Occupational Medicine and Environmental Health,Key Laboratory of Modern Toxicology of Ministry of Education,School of Public Health,Nanjing Medical University,Nanjing,Jiangsu 211166,China;Department of Public Health,Kangda College of Nanjing Medical University,Lianyungang,Jiangsu 222000,China
摘要：Silicosis is an occupational lung disease caused by prolonged exposure to silica dust in the workplace.It has a complex pathogenesis and currently lacks effective treatments.Homoharringtonine(HHT)is a natural compound approved for the treatment of acute myeloid leukemia,but its effects on silicosis remain unclear.In the present study,we constructed a mouse model of silica(SiO2)-induced pulmonary fibrosis and evaluated the preventive and therapeutic effects of HHT.The results showed that HHT significantly attenuated the progression of SiO2-induced pulmonary fibrosis in mice.We then used MRC-5,a human lung fibroblast cell line,to explore the mechanisms underlying HHT's inhibitory effects in vitro and found that HHT significantly inhibited the activation and migratory capacity of MRC-5 cells.Mechanistically,these effects were mediated by enhanced ubiquitination and degradation of the CCR1 protein.Furthermore,HHT exhibited favorable biocompatibility in vivo,and its preventive and therapeutic effects were validated in SiO2-treated mice.Collectively,the current study demonstrates that HHT shows significant potential as a therapeutic agent for silicosis by targeting CCR1 and the PI3K/AKT/mTOR signaling pathway,highlighting it as a promising candidate for clinical translation for silicosis treatment.
机标关键词：pathwaysringharrhomoanti-silicosiseffectsexertsfibroblasts
分类号：R135.2(劳动卫生)
论文发表日期：2025-11-30
在线出版日期：2026-01-15（本平台首次上网日期，不代表文献的发表时间）
页数：18( 622-638,中插22-中插28 )
英文信息