Bmi-1 alleviates adventitial fibroblast senescence by eliminating ROS in pulmonary hypertension

Kai Li, Yan Li, Youjia Yu, Jingjing Ding, Huijie Huang, Chunyan Chu, Li Hu, Yanfang Yu, Yue Cao, Peng Xu, David Fulton, Feng Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Pulmonary hypertension (PH) is a life-threatening progressive disease with high mortality in the elderly. However, the pathogenesis of PH has not been fully understood and there is no effective therapy to reverse the disease process. This study aims to determine whether cellular senescence is involved in the development of PH. Methods: The rat PH model was established by intraperitoneal injection of monocrotaline and evaluated by pulmonary arteriole wall thickness and right ventricular hypertrophy index. Human lung fibroblasts (HLFs) were treated with CoCl2 or hypoxia to induce cellular senescence in vitro. SA-β-gal staining and the changes of senescent markers were used to examine cellular senescence. The molecular mechanism of cellular senescence was further explored by detecting reactive oxygen species (ROS) levels and culturing cells with a conditioned medium. Results: We revealed the cellular senescence of pulmonary adventitial fibroblasts in vivo in the rat PH model. The expression of Bmi-1, an important regulator of senescence, was decreased in the lungs of PH rats and localized in adventitial fibroblasts. The in vitro experiments showed that p16 expression was increased while Bmi-1 expression was decreased after CoCl2 treatment in HLFs. Mechanistically, Bmi-1 could alleviate CoCl2-induced HLFs senescence by eliminating ROS which further promoted the proliferation of pulmonary artery smooth muscle cells by paracrine mode of action of HLFs. Conclusion: Bmi-1 alleviates the cellular senescence of pulmonary fibroblasts in PH, which expands the pathogenesis of PH and provides a theoretical basis for targeting senescent cells in the treatment of PH.

Original languageEnglish (US)
Article number80
JournalBMC Pulmonary Medicine
Volume21
Issue number1
DOIs
StatePublished - Dec 2021

Keywords

  • Bmi-1
  • Lung fibroblast
  • Oxidative stress
  • Pulmonary hypertension
  • Senescence

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Fingerprint

Dive into the research topics of 'Bmi-1 alleviates adventitial fibroblast senescence by eliminating ROS in pulmonary hypertension'. Together they form a unique fingerprint.

Cite this