Late Breaking Oral Abstract Australasian Extracellular Vesicles Conference 2018

Mechanical force differentially regulates EV-miRNAs in lung epithelial cell (#32)

Tanbir Najrana 1 2 , Elena Kreienberg 1 , Victoria Schulte 1 , Christoph Schorl 1 , Juan Sanchez-Esteban 3
  1. Brown University, Providence, USA, Providence, RHODE ISLAND, United States
  2. Women and Infants Hospital, The Alpert Medical School of Brown University, Providence, Rhode Island, United States
  3. Pediatrics, Women and Infants Hospital, the Alpert Medical School of Brown University, Providence, Rhode Island, United States

Introduction: Extracellular vesicles (EVs) are membrane-bound particles released by many cells. They are rich in miRNA and other bioactive molecules and regulate cell signaling during tissue development. The role of EVs in fetal lung development is unexplored. Incomplete development of the lung can cause severe neonatal morbidity and mortality. Lung morphogenesis depends on mechanical signals. However, the mechanism by which mechanical force promotes lung development is not well-characterized. miRNAs have been shown to play critical roles in cell signaling during fetal lung development. Given that physiological mechanical signals release EV, and miRNAs key components of the EVs cargo, we hypothesize that mechanical force induced EV-miRNA promote fetal lung development.

Methods: MLE-12 cells, a murine cell line of alveolar type II epithelial cells, were exposed to cyclic or continuous mechanical stretch for 24 hours to mimic mechanical signals in fetal lung development. Cells under static conditions were used as control. EVs were isolated from condition medium using differential centrifugation. Size and quantification of EVs were determined by Nano Sight device. Total RNAs isolated from EVs were used to analyze miRNA profile by micro-array assay.

Results: Several miRNAs including miRNA-let-c, miRNA-188, miRNA24-2 and miRNA-23d (p values between 3E-05 to 0.008) were upregulated after mechanical stretch.

Conclusions: Mechanical signal enhances the release EV-miRNA in MLE12. Given the role of these miRNAs in cellular differentiation, proliferation, apoptosis and growth regulation, we speculate that stretch-mediated EV-miRNA plays a role during fetal lung development. We are currently testing the speculation using primary fetal epithelial cells.