title: MicroRNA-146a modulates human bronchial epithelial cell survival in response to the cytokine-induced apoptosis.
abstract: 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.
authors.affiliation: 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
authors.forename: Xiangde
authors.initials: X
authors.lastname: Liu
authors.forename: Amy
authors.initials: A
authors.lastname: Nelson
authors.forename: Xingqi
authors.initials: X
authors.lastname: Wang
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kanaji
authors.forename: Miok
authors.initials: M
authors.lastname: Kim
authors.forename: Tadashi
authors.initials: T
authors.lastname: Sato
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakanishi
authors.forename: YingJi
authors.initials: Y
authors.lastname: Li
authors.forename: Jianhong
authors.initials: J
authors.lastname: Sun
authors.forename: Joel
authors.initials: J
authors.lastname: Michalski
authors.forename: Amol
authors.initials: A
authors.lastname: Patil
authors.forename: Hesham
authors.initials: H
authors.lastname: Basma
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Rennard
mesh_terms: 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
chemical_list: C494811:BCL2L1 protein, human; D016207:Cytokines; C542542:MIRN146 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D051020:bcl-X Protein