TGF?1 Archives - World Asthma Foundation

MiR-23b controls TGF-?1 induced airway smooth muscle cell proliferation via TGF?R2/p-Smad3 signals.

Mol Immunol. 2015 Dec 31;70:84-93

Authors: Chen M, Huang L, Zhang W, Shi J, Lin X, Lv Z, Zhang W, Liang R, Jiang S

Abstract
BACKGROUND: Abnormal proliferation of ASM (airway smooth muscle) directly contributes to the airway remodeling during development of lung diseases such as asthma. Here we report that a specific microRNA (miR-23b) controls ASMCs proliferation through directly inhibiting TGF?R2/p-Smad3 pathway.
METHODS: The expression of miR-23b in ASMCs was detected by quantitative real-time polymerase chain reaction (RT-PCR). The effects of miR-23b on cell proliferation and apoptosis of ASMCs were assessed by transient transfection of miR-23b mimics and inhibitor. The target gene of miR-23b and the downstream pathway were further investigated.
RESULTS: Overexpression of miR-23b significantly inhibited TGF-?1-induced ASMCs proliferation and promoted apoptosis. RT-PCR and Western blotting analysis showed miR-23b negatively regulates the expression of TGF?R2 and p-Smad3 in ASMCs. Subsequent analyses demonstrated that TGF?R2 was a direct and functional target of miR-23b, which was validated by the dual luciferase reporter assay.
CONCLUSIONS: MiR-23b may function as an inhibitor of airway smooth muscle cells proliferation through inactivation of TGF?R2/p-Smad3 pathway.

PMID: 26748386 [PubMed – as supplied by publisher]

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Allergen-Induced Coexpression of bFGF and TGF-?1 by Macrophages in a Mouse Model of Airway Remodeling: bFGF Induces Macrophage TGF-?1 Expression in vitro.

Int Arch Allergy Immunol. 2010 Nov 25;155(1):12-22

Authors: Yum HY, Cho JY, Miller M, Broide DH

Background: Basic fibroblast growth factor (bFGF) is a cytokine that is mitogenic for fibroblasts and smooth muscle and may play a role in airway remodeling in asthma. We have used a mouse model of chronic ovalbumin (OVA) allergen-induced airway remodeling to determine whether bFGF and fibroblast growth factor receptor-1 are expressed and regulated by corticosteroids in the airway, as well as to determine whether bFGF mediates expression of another proremodeling cytokine, transforming growth factor (TGF)-?1. Methods: The airway levels and localization of bFGF, FGF receptor-1 and TGF-?1 were determined by ELISA, immunohistology and image analysis in the remodeled airways of chronic OVA-challenged mice treated with either corticosteroids or diluent. In vitro cultures of bone narrow-derived macrophages were used to determine whether bFGF induced TGF-?1 expression. Results: Mice chronically challenged with OVA developed significant airway remodeling that was associated with significantly increased levels of bFGF and TGF-?1. Immunohistochemistry demonstrated significantly increased bFGF and FGF receptor-1 expression by peri- bronchial F4/80+ cells. Double-label immunofluorescence microscopy studies demonstrated that peribronchial macrophages coexpressed bFGF and TGF-?1. In vitro studies demonstrated that incubation of bone marrow-derived macrophages with bFGF induced expression of TGF-?1. Mice treated with corticosteroids and subjected to chronic OVA challenge had significantly reduced levels of bFGF, FGF receptor-1, peribronchial TGF-?1+ cells and airway remodeling. Conclusions: Overall, this study demonstrates that allergen challenge stimulates peribronchial macrophages to coexpress bFGF and TGF-?1 and that bFGF may potentiate macrophage release of TGF-?1 through autocrine and/or paracrine pathways.

PMID: 21109744 [PubMed – as supplied by publisher]

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