2
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Cellular senescence and EMT crosstalk in bleomycin-induced pathogenesis of pulmonary fibrosis-an in vitro analysis.

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          With poor prognosis and aberrant lung remodeling, pulmonary fibrosis exhibits worldwide prevalence accompanied by an increase in burden in terms of hospitalization and death. Apart from genetic and non-genetic factors, fibrosis occurs as a side effect of bleomycin antineoplastic activity. Elucidating the cellular and molecular mechanism could help in the development of effective anti-fibrotic treatment strategies. In the present study, we investigated the underlying mechanism behind bleomycin-induced fibrosis using human alveolar epithelial cells (A549 cells). On the basis of the experimental observation, it was demonstrated that with transforming growth factor-β (TGF-β) as a central mediator of fibrosis progression, a cross-talk between epithelial-mesenchymal transition (EMT) and senescence upon bleomycin treatment occurs. This results in the advancement of this serious fibrotic condition. Fibrosis was initiated through integrin activation and imbalance in the redox state (NOX expression) of the cell. It progressed along the TGF-β-mediated non-canonical pathway (via ERK phosphorylation) followed by the upregulation of α-smooth muscle actin and collagen synthesis. Additionally, in this process, the loss of the epithelial marker E-cadherin was observed. Furthermore, the expressions of senescence markers, such as p21 and p53, were upregulated upon bleomycin treatment, thereby intensifying the fibrotic condition. Accordingly, the molecular pathway mediating the bleomycin-induced fibrosis was explored in the current study.

          Related collections

          Author and article information

          Journal
          Cell Biol Int
          Cell biology international
          Wiley
          1095-8355
          1065-6995
          Feb 2020
          : 44
          : 2
          Affiliations
          [1 ] Department of Biochemistry, School of Medicine, Jeju National University, Jeju, 63243, Republic of Korea.
          [2 ] Institute of Medical Science, Jeju National University, Jeju, 63241, Republic of Korea.
          [3 ] Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju, 63241, Republic of Korea.
          Article
          10.1002/cbin.11248
          31631444
          0693c506-de66-4f24-a24b-c617d7b7405a
          © 2019 International Federation for Cell Biology.
          History

          NOX,TGF-β,bleomycin,redox imbalance,senescence
          NOX, TGF-β, bleomycin, redox imbalance, senescence

          Comments

          Comment on this article