International Journal of COPD (Apr 2023)

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

  • Wang W,
  • Zhang S,
  • Cui L,
  • Chen Y,
  • Xu X,
  • Wu L

Journal volume & issue
Vol. Volume 18
pp. 533 – 539

Abstract

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Weimin Wang,1,* Shaohong Zhang,1,* Lei Cui,2 Yu Chen,2 Xingxing Xu,2 Longchuan Wu2 1Department of Gerontology, The Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University, Huaian, People’s Republic of China; 2Department of Respiratory Medicine, Huaian Hospital of Traditional Chinese Medicine, Affiliated to Nanjing University of Traditional Chinese Medicine, Huaian, People’s Republic of China*These authors contributed equally to this workCorrespondence: Longchuan Wu; Xingxing Xu, Email [email protected]; [email protected]: 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

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