Department of Gerontology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huaian, People's Republic of China.
Department of Respiratory Medicine, Huaian Hospital of Traditional Chinese Medicine, Affiliated to Nanjing University of Traditional Chinese Medicine, Huaian, People's Republic of China.
Int J Chron Obstruct Pulmon Dis. 2023 Apr 8;18:533-539. doi: 10.2147/COPD.S383295. eCollection 2023.
Bufei Yishen formula (BYF) is an effective prescription for the clinical treatment of chronic obstructive pulmonary disease (COPD). However, the molecular mechanism by which it exerts its pharmacological effects remains to be explored.
The human bronchial cell line BEAS-2B was treated with cigarette smoke extract (CSE). Cellular senescence markers were detected by Western blot and ELISA. Potential transcription factor of klotho was predicted using JASPAR and USCS databases.
CSE induced cellular senescence with intracellular accumulation of cellular senescence biomarkers (p16, p21 and p27) and increased secretion of senescence-related secretory phenotypic (SASP) factors (IL-6, IL-8, and CCL3). In contrast, BYF treatment inhibited CSE-induced cellular senescence. CSE suppressed the transcription, expression and secretion of klotho, whereas BYF treatment rescued its transcription, expression and secretion. CSE downregulated the protein level of ZNF263, whereas BYF treatment rescued the expression of ZNF263. Furthermore, ZNF263-overexpressing BEAS-2B cells could inhibit CSE-induced cellular senescence and SASP factor secretion by upregulating the expression of klotho.
This study revealed a novel pharmacological mechanism by which BYF alleviates clinical symptoms of COPD patients, and regulating ZNF263 and klotho expression may be beneficial to the treatment and prevention of COPD.
补肺益肾方（BYF）是治疗慢性阻塞性肺疾病（COPD）的有效方剂。然而，其发挥药理作用的分子机制仍有待探索。
用香烟烟雾提取物（CSE）处理人支气管细胞系 BEAS-2B。通过 Western blot 和 ELISA 检测细胞衰老标志物。使用 JASPAR 和 USCS 数据库预测 klotho 的潜在转录因子。
CSE 诱导细胞衰老，细胞内衰老生物标志物（p16、p21 和 p27）积累，衰老相关分泌表型（SASP）因子（IL-6、IL-8 和 CCL3）分泌增加。相反，BYF 处理抑制 CSE 诱导的细胞衰老。CSE 抑制 klotho 的转录、表达和分泌，而 BYF 处理挽救了其转录、表达和分泌。CSE 下调 ZNF263 的蛋白水平，而 BYF 处理挽救了 ZNF263 的表达。此外，过表达 ZNF263 的 BEAS-2B 细胞可以通过上调 klotho 的表达来抑制 CSE 诱导的细胞衰老和 SASP 因子分泌。
本研究揭示了 BYF 缓解 COPD 患者临床症状的新的药理机制，调节 ZNF263 和 klotho 的表达可能有益于 COPD 的治疗和预防。
