Maresin-1 regulates epithelial to mesenchymal transition and wound healing processes in bronchial epithelial cells

Details

• Personal Author:
  Bailey KL ; Heires AJ ; Nordgren TM ; Romberger DJ
• Description:
  Rationale: In the airway epithelium, epithelial to mesenchymal transition (EMT) can be a reparative or pathologic process, depending on the activation stimulus and regulatory cues governing the process. Pro-resolving lipid mediators have recently been implicated as both positive and negative regulators of EMT-related pathways. We sought to determine how the pro-resolving lipid mediator maresin-1 (MaR1) regulates the EMT response to pro-inflammatory stimuli in bronchial epithelial cells. Methods: Primary human bronchial epithelial cells or the transformed bronchial epithelial cell line BEAS-2B were stimulated with 5 ng/mL TGF-B1 in the presence or absence of 1 - 100 nM MaR1. Cultures were assessed over 96 hours to ascertain how MaR1 treatment altered TGF-B1-induced EMT. Western blotting and gel zymography were performed to ascertain protein expression and protease activities, and confluent cultures were wounded and wound closure was monitored. Results: TGF-B1-treated cultures exhibited morphological changes of mesenchymal transition by 72 hr following treatment. These changes correlated with loss of E-cadherin expression and increased fibronectin, MMP-2 and MMP-9 release. However, TGF-B1-induced loss of E-cadherin expression was repressed by 1 nM MaR1 treatment, and 100 nM MaR1 reduced TGF-B1 induction of fibronectin production. TGF-B1 increased MMP-2 protein expression and protease activities nearly two-fold, while cultures treated with MaR1 exhibited MMP-2 protease activities similar to controls. Despite inhibiting E-cadherin loss and MMP-2 protease activities, MaR1 did not impair TGF-B1-mediated increased wound healing capacity, and MaR1 treatment alone increased wound healing as compared to untreated, wounded cultures. Conclusions: Our results suggest the pro-resolving lipid mediator MaR1 regulates the bronchial epithelial response to inflammation and wounding, encouraging maintenance of epithelial programing during non-injurious inflammatory insults, and speeding healing following wounding. [Description provided by NIOSH]
• Subjects:
  Lipids Occupational Health Pathology Safety
• Keywords:
  Cell Biology Cell Function Cellular Function Humans Morphology Proteins
• ISSN:
  1073-449X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  193
• NIOSHTIC Number:
  nn:20048504
• Citation:
  Am J Respir Crit Care Med 2016 May; 193(Abstract Issue):A5896
• Email:
  tnordgren@unmc.edu
• Federal Fiscal Year:
  2016
• Performing Organization:
  University of Nebraska Medical Center, Omaha, Nebraska
• Peer Reviewed:
  False
• Start Date:
  20060801
• Source Full Name:
  American Journal of Respiratory and Critical Care Medicine
• Supplement:
  Abstract Issue
• End Date:
  20160731
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:345018ad3b86333d6c71252556185b9f6270823d19a11243c00cf64363d8f9cc1b66422bec6c26a4e52394e04eb39d4dc37851b7167feedeb20e1641c60e86a5
• Download URL:
  https://stacks.cdc.gov/view/cdc/203247/cdc_203247_DS1.pdf
• File Type:
  [PDF - 16.92 KB ]