TY - JOUR T1 - miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.00138-2019 VL - 5 IS - 4 SP - 00138-2019 AU - Silvia Moimas AU - Francesco Salton AU - Beata Kosmider AU - Nadja Ring AU - Maria C. Volpe AU - Karim Bahmed AU - Luca Braga AU - Michael Rehman AU - Simone Vodret AU - Maria Laura Graziani AU - Marla R. Wolfson AU - Nathaniel Marchetti AU - Thomas J. Rogers AU - Mauro Giacca AU - Gerard J. Criner AU - Serena Zacchigna AU - Marco Confalonieri Y1 - 2019/10/01 UR - http://openres.ersjournals.com/content/5/4/00138-2019.abstract N2 - 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 ER -