Bufei Yishen Formula Inhibits the Cell Senescence in COPD by Up-Regulating the ZNF263 and Klotho Expression

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords:

• Bufei Yishen formula
• cell senescence
• ZNF263
• klotho
• senescence-related secretory phenotypic

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Acknowledgments

This work was supported by Huai’an Science and Technology Bureau (No. HAB202037), the Innovation Service Capacity Building Program of Huai’an (No. HAP202003), Special fund of Huai’an Science and Technology Bureau: Huai’an Key Laboratory of Geriatric Diseases and Geriatric Syndrome (No. HAP202105) and The research project of elderly health in Jiangsu Province (No. LR2021050). Weimin Wang and Shaohong Zhang are co-first authors for this study. Longchuan Wu and Xingxing Xu are co-correspondence authors for this study.

Disclosure

The authors declare no competing interests in this work.

Additional information

Funding

This work was supported by Huai’an Science and Technology Bureau (No. HAB202037), the Innovation Service Capacity Building Program of Huai’an (No. HAP202003), Special fund of Huai’an Science and Technology Bureau: Huai’an Key Laboratory of Geriatric Diseases and Geriatric Syndrome (No. HAP202105) and The research project of elderly health in Jiangsu Province (No. LR2021050).