Let-7d microRNA affects mesenchymal phenotypic properties of lung fibroblasts.
MicroRNAs are small noncoding RNAs that inhibit protein expression. We have previously shown that the inhibition of the microRNA let-7d in epithelial cells caused changes consistent with epithelial-to-mesenchymal transition (EMT) both in vitro and in vivo. The aim of this study was to determine whether the introduction of let-7d into fibroblasts alters their mesenchymal properties. Transfection of primary fibroblasts with let-7d caused a decrease in expression of the mesenchymal markers α-smooth muscle actin, N-cadherin, fibroblast-specific protein-1, and fibronectin, as well as an increase in the epithelial markers tight junction protein-1 and keratin 19. Phenotypic changes were also present, including a delay in wound healing, reduced motility, and proliferation of fibroblasts following transfection. In addition, we examined the effects of transfection on fibroblast responsiveness to TGF-β, an important factor in many fibrotic processes such as lung fibrosis and found that let-7d transfection significantly attenuated high-mobility group-A2 protein induction by TGF-β. Our results indicate that administration of the epithelial microRNA let-7d can significantly alter the phenotype of primary fibroblasts.
Yale Univ., School of Medicine, 300 Cedar St., TAC-441 South, New Haven, CT 06520. naftali.kaminski@yale.edu.
Luai
L
Huleihel
Ahmi
A
Ben-Yehudah
Jadranka
J
Milosevic
Guoying
G
Yu
Kusum
K
Pandit
Koji
K
Sakamoto
Hanadie
H
Yousef
Megan
M
LeJeune
Tiffany A
TA
Coon
Carrie J
CJ
Redinger
Lara
L
Chensny
Ester
E
Manor
Gerald
G
Schatten
Naftali
N
Kaminski
D000199:Actins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism; D025743:HMGA2 Protein / Q000378:metabolism; D024261:HMGB2 Protein / Q000378:metabolism; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000378:metabolism / Q000473:pathology; D053539:Keratin-19 / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D058628:Myofibroblasts / Q000378:metabolism*; D011650:Pulmonary Alveoli / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000235:genetics / Q000378:metabolism*; D000071999:S100 Calcium-Binding Protein A4; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014945:Wound Healing / Q000235:genetics; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
C541116:ACTA2 protein, human; D000199:Actins; D015820:Cadherins; D002135:Calcium-Binding Proteins; D005353:Fibronectins; D025743:HMGA2 Protein; D024261:HMGB2 Protein; D053539:Keratin-19; D035683:MicroRNAs; D000071999:S100 Calcium-Binding Protein A4; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D062826:Zonula Occludens-1 Protein; C487931:mirnlet7 microRNA, human; C077591:S100A4 protein, human
Slug; epithelial-to-mesenchymal transition; fibrosis; high-mobility group-A2 protein; idiopathic pulmonary fibrosis; microRNA; transforming growth factor-β