miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation.
Journal
ERJ open research
ISSN: 2312-0541
Titre abrégé: ERJ Open Res
Pays: England
ID NLM: 101671641
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
05
06
2019
accepted:
23
09
2019
entrez:
21
12
2019
pubmed:
21
12
2019
medline:
21
12
2019
Statut:
epublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 31857992
doi: 10.1183/23120541.00138-2019
pii: 00138-2019
pmc: PMC6911923
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL118171
Pays : United States
Informations de copyright
Copyright ©ERS 2019.
Déclaration de conflit d'intérêts
Conflict of interest: S. Moimas has nothing to disclose. Conflict of interest: F. Salton has nothing to disclose. Conflict of interest: B. Kosmider has nothing to disclose. Conflict of interest: N. Ring has nothing to disclose. Conflict of interest: M.C. Volpe has nothing to disclose. Conflict of interest: K. Bahmed has nothing to disclose. Conflict of interest: L. Braga has nothing to disclose. Conflict of interest: M. Rehman has nothing to disclose. Conflict of interest: S. Vodret has nothing to disclose. Conflict of interest: M.L. Graziani has nothing to disclose. Conflict of interest: M.R. Wolfson has nothing to disclose. Conflict of interest: N. Marchetti has nothing to disclose. Conflict of interest: T.J. Rogers has nothing to disclose. Conflict of interest: M. Giacca has nothing to disclose. Conflict of interest: G.J. Criner has nothing to disclose. Conflict of interest: S. Zacchigna has nothing to disclose. Conflict of interest: M. Confalonieri has nothing to disclose.
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