Patarat Rathasapa, Chuaybudda Suchanart, Yasom Sakawdaurn, Mutirangura Apiwat
Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University, King Chulalongkorn Memorial Hospital, Bangkok, 10330, Thailand.
Interdisciplinary Program of Biomedical Sciences, Graduate School, Chulalongkorn University, Bangkok, Thailand.
BMC Pulm Med. 2025 Jan 31;25(1):52. doi: 10.1186/s12890-025-03522-2.
Pulmonary fibrosis is characterized by the destruction of normal lung tissue and then replacement by abnormal fibrous tissue, leading to an overall decrease in gas exchange function. The effective treatment for pulmonary fibrosis remains unknown. The upstream pathogenesis of pulmonary fibrosis may involve cellular senescence of the lung tissue. Previously, a new gene therapy technology using Box A of the HMGB1 plasmid (Box A) was used to reverse cellular senescence and cure liver fibrosis in aged rats.
Here, we show that Box A is a promising medicine for the treatment of lung fibrosis. In a bleomycin-induced pulmonary fibrosis model in the male Wistar rats, Student's t-test and one-way ANOVA were used to compare groups of samples.
Box A effectively lowered fibrous tissue deposits (from 18.74 ± 0.62 to 3.45 ± 1.19%) and senescent cells (from 3.74 ± 0.40% to 0.89 ± 0.18%) to levels comparable to those of the negative control group. Moreover, after eight weeks, Box A also increased the production of the surfactant protein C (from 3.60 ± 1.68% to 6.82 ± 0.65%).
Our results demonstrate that Box A is a promising therapeutic approach for pulmonary fibrosis and other senescence-promoted fibrotic lesions.
肺纤维化的特征是正常肺组织遭到破坏，随后被异常纤维组织取代，导致气体交换功能整体下降。肺纤维化的有效治疗方法仍不明确。肺纤维化的上游发病机制可能涉及肺组织的细胞衰老。此前，一种使用高迁移率族蛋白B1质粒的A盒（A盒）的新型基因治疗技术被用于逆转细胞衰老并治愈老年大鼠的肝纤维化。
在此，我们表明A盒是一种有前景的治疗肺纤维化的药物。在雄性Wistar大鼠博来霉素诱导的肺纤维化模型中，采用学生t检验和单因素方差分析对样本组进行比较。
A盒有效降低了纤维组织沉积（从18.74±0.62%降至3.45±1.19%）和衰老细胞（从3.74±0.40%降至0.89±0.18%），使其水平与阴性对照组相当。此外，八周后，A盒还增加了表面活性蛋白C的产生（从3.60±1.68%增至6.82±0.65%）。
我们的结果表明，A盒是一种有前景的治疗肺纤维化及其他衰老促进的纤维化病变的方法。
