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AKT2 regulates pulmonary inflammation and fibrosis via modulating macrophage activation
Nie Y.5; Sun L.5; Wu Y.5; Yang Y.5; Wang J.5; He H.5; Hu Y.5; Chang Y.3; Liang Q.5; Zhu J.5; Ye R.D.5; Christman J.W.4; Qian F.5
2017-06-01
Source PublicationJournal of Immunology
ISSN15506606 00221767
Volume198Issue:11Pages:4470-4480
AbstractIdiopathic pulmonary fibrosis (IPF) is a highly lethal pathological process that is characterized by inflammation, fibroblast accumulation, and excessive collagen deposition. Although AKT2-mediated signaling pathways modulate inflammatory responses, their role in IPF has not been defined. We report that AKT2 deficiency (Akt22/2) protected against bleomycin-induced pulmonary fibrosis and inflammation. Adoptive transfer of wild-type macrophages or administration of IL-13 to Akt22/2 mice could restore pulmonary fibrosis. In response to IL-33 treatment, Akt22/2 macrophages displayed decreased production of IL-13 and TGF-b1 and attenuated phosphorylation of FoxO3a compared with Akt2+/+ macrophages. Furthermore, the expression of IL-13 was increased by small interfering RNA knockdown of FoxO3a or in FoxO3a-deficient macrophages. By evaluating lung sections from pulmonary fibrosis patients, we found that the phosphorylation of AKT2 and FoxO3a was remarkably upregulated. Collectively, these results indicate that AKT2 modulates pulmonary fibrosis through inducing TGF-b1 and IL-13 production by macrophages, and inhibition of AKT2 may be a potential strategy for treating IPF.
DOI10.4049/jimmunol.1601503
URLView the original
Language英語
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Cited Times [WOS]:20   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Cancer Institute and Hospital, Chinese Academy of Medical Sciences
2.Bengbu Medical College
3.Nanjing Medical University
4.Ohio State University
5.Shanghai Jiao Tong University
6.University of Macau
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GB/T 7714
Nie Y.,Sun L.,Wu Y.,et al. AKT2 regulates pulmonary inflammation and fibrosis via modulating macrophage activation[J]. Journal of Immunology,2017,198(11):4470-4480.
APA Nie Y..,Sun L..,Wu Y..,Yang Y..,Wang J..,...&Qian F..(2017).AKT2 regulates pulmonary inflammation and fibrosis via modulating macrophage activation.Journal of Immunology,198(11),4470-4480.
MLA Nie Y.,et al."AKT2 regulates pulmonary inflammation and fibrosis via modulating macrophage activation".Journal of Immunology 198.11(2017):4470-4480.
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