The role of SerpinB2 in human bronchial epithelial cells responses to particulate matter exposure.

Abstract:

:Exposure to particulate matter (PM) has been related to the onset of adverse health effects including lung cancer, but the underlying molecular mechanisms are still under investigation. Epithelial-to-mesenchymal transition (EMT) is regarded as a crucial step in cancer progression. In a previous study, we reported EMT-related responses in the human bronchial epithelial cell line HBEC3-KT, exposed to Milan airborne winter PM2.5. We also found a strong modulation of SERPINB2, encoding for the PAI-2 protein and previously suggested to play an important role in cancer. Here we investigate the role of SERPINB2/PAI-2 in the regulation of EMT-related effects induced by PM exposure in HBEC3-KT. PM exposure (up to 10 µg/cm2) increased SERPINB2 expression, reduced cell migration and induced morphological alterations in HBEC3-KT. Changes in actin structure and cadherin-1 relocalization were observed in PM-exposed samples. Knockdown of SERPINB2 by siRNA down-regulated the CDH1 gene expression, as well as PAI-2 and cadherin-1 protein expression. SERPINB2 knockdown also increased cell migration rate, and counteracted the PM-induced reduction of cell migration and alteration of cell morphology. SERPINB2 was found to be greatly down-regulated in a HBEC2-KT transformed cell line, supporting the importance of this gene in the regulation of EMT. In conclusion, here we show that PAI-2 regulates CDH1 gene/cadherin-1 protein expression in bronchial HBEC3-KT cells, and this mechanism might be involved in the regulation of cell migration. SERPINB2 down-regulation should be considered part of EMT, and the over-expression of SERPINB2 in PM-exposed samples might be interpreted as an initial protective mechanism.

journal_name

Arch Toxicol

journal_title

Archives of toxicology

authors

Longhin E,Camatini M,Bersaas A,Mantecca P,Mollerup S

doi

10.1007/s00204-018-2259-z

subject

Has Abstract

pub_date

2018-09-01 00:00:00

pages

2923-2933

issue

9

eissn

0340-5761

issn

1432-0738

pii

10.1007/s00204-018-2259-z

journal_volume

92

pub_type

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