RT Journal Article
SR Electronic
T1 miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00138-2019
DO 10.1183/23120541.00138-2019
VO 5
IS 4
A1 Silvia Moimas
A1 Francesco Salton
A1 Beata Kosmider
A1 Nadja Ring
A1 Maria C. Volpe
A1 Karim Bahmed
A1 Luca Braga
A1 Michael Rehman
A1 Simone Vodret
A1 Maria Laura Graziani
A1 Marla R. Wolfson
A1 Nathaniel Marchetti
A1 Thomas J. Rogers
A1 Mauro Giacca
A1 Gerard J. Criner
A1 Serena Zacchigna
A1 Marco Confalonieri
YR 2019
UL http://openres.ersjournals.com/content/5/4/00138-2019.abstract
AB Rationale Alveolar type II (ATII) cells act as adult stem cells contributing to alveolar type I (ATI) cell renewal and play a major role in idiopathic pulmonary fibrosis (IPF), as supported by familial cases harbouring mutations in genes specifically expressed by these cells. During IPF, ATII cells lose their regenerative potential and aberrantly express pathways contributing to epithelial–mesenchymal transition (EMT). The microRNA miR-200 family is downregulated in IPF, but its effect on human IPF ATII cells remains unproven. We wanted to 1) evaluate the characteristics and transdifferentiating ability of IPF ATII cells, and 2) test whether miR-200 family members can rescue the regenerative potential of fibrotic ATII cells.Methods ATII cells were isolated from control or IPF lungs and cultured in conditions promoting their transdifferentiation into ATI cells. Cells were either phenotypically monitored over time or transfected with miR-200 family members to evaluate the microRNA effect on the expression of transdifferentiation, senescence and EMT markers.Results IPF ATII cells show a senescent phenotype (p16 and p21), overexpression of EMT (ZEB1/2) and impaired expression of ATI cell markers (AQP5 and HOPX) after 6 days of culture in differentiating medium. Transfection with certain miR-200 family members (particularly miR-200b-3p and miR-200c-3p) reduced senescence marker expression and restored the ability to transdifferentiate into ATI cells.Conclusions We demonstrated that ATII cells from IPF patients express senescence and EMT markers, and display a reduced ability to transdifferentiate into ATI cells. Transfection with certain miR-200 family members rescues this phenotype, reducing senescence and restoring transdifferentiation marker expression.Idiopathic pulmonary fibrosis alveolar epithelial type II cells show senescence and EMT features, but miR-200b and miR-200c can restore the ability of type II cells to transdifferentiate in vitro into type I alveolar epithelial cells http://bit.ly/359tlit