MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis.
MicroRNA plays an important role in cell differentiation, proliferation and cell death. The current study found that miRNA-146a was up-regulated in human bronchial epithelial cells (HBECs) in response to stimulation by TGF-beta1 plus cytomix (a mixture of IL-1beta, IFN-gamma and TNF-alpha). TGF-beta1 plus cytomix (TCM) induced apoptosis in HBECs (3.4+/-0.6% of control vs 83.1+/-4.0% of TCM treated cells, p<0.01), and this was significantly blocked by the miRNA-146a mimic (8.8+/-1.5%, p<0.01). In contrast, a miRNA-146a inhibitor had only a modest effect on cell survival but appeared to augment the induction of epithelial-mesenchymal transition (EMT) in response to the cytokines. The MicroRNA-146a mimic appears to modulate HBEC survival through a mechanism of up-regulating Bcl-XL and STAT3 phosphorylation, and by this mechanism it could contribute to tissue repair and remodeling.
Liu
Xiangde
X
Pulmonary, Critical Care, Sleep and Allergy Medicine, Department of Internal Medicine, University of Nebraska Medical Center, 985885 Nebraska Medical Center, Omaha, NE 68198-5885, USA. xdliu@unmc.edu
Nelson
Amy
A
Wang
Xingqi
X
Kanaji
Nobuhiro
N
Kim
Miok
M
Sato
Tadashi
T
Nakanishi
Masanori
M
Li
YingJi
Y
Sun
Jianhong
J
Michalski
Joel
J
Patil
Amol
A
Basma
Hesham
H
Rennard
Stephen I
SI
D017209:Apoptosis / Q000235:genetics; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics; D016207:Cytokines / Q000494:pharmacology / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism
C494811:BCL2L1 protein, human; D016207:Cytokines; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051020:bcl-X Protein