Title :

Endogenous Semaphorin-7A Impedes Human Lung Fibroblast Differentiation

Author(s) :

Esnault, Stéphane [Auteur]
University of Wisconsin School of Medicine and Public Health
Torr, Elizabeth E [Auteur]
Bernau, Ksenija [Auteur]
Johansson, Mats W [Auteur]
Kelly, Elizabeth A [Auteur]
Sandbo, Nathan [Auteur]
Jarjour, Nizar N [Auteur]

Journal title :

PLoS ONE

Abbreviated title :

PLoS One

Volume number :

12

Pages :

e0170207

Publication date :

2017-01-17

ISSN :

1932-6203

English keyword(s) :

Animals
Cell Differentiation
Cells, Cultured
Extracellular Matrix
Fibroblasts
Fibronectins
Humans
Idiopathic Pulmonary Fibrosis
Lung
Mice
NIH 3T3 Cells
Pulmonary Fibrosis
Semaphorins
Transforming Growth Factor beta1

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Semaphorin-7A is a glycosylphosphatidylinositol-anchored protein, initially characterized as an axon guidance protein. Semaphorin-7A also contributes to immune cell regulation and may be an essential pro-fibrotic factor ...
Show more >Semaphorin-7A is a glycosylphosphatidylinositol-anchored protein, initially characterized as an axon guidance protein. Semaphorin-7A also contributes to immune cell regulation and may be an essential pro-fibrotic factor when expressed by non-fibroblast cell types (exogenous). In mouse models, semaphorin-7A was shown to be important for TGF-ß1-induced pulmonary fibrosis characterized by myofibroblast accumulation and extracellular matrix deposition, but the cell-specific role of semaphorin-7A was not examined in fibroblasts. The purpose of this study is to determine semaphorin-7A expression by fibroblasts and to investigate the function of endogenously expressed semaphorin-7A in primary human lung fibroblasts (HLF). Herein, we show that non-fibrotic HLF expressed high levels of cell surface semaphorin-7A with little dependence on the percentage of serum or recombinant TGF-ß1. Semaphorin-7A siRNA strongly decreased semaphorin-7A mRNA expression and reduced cell surface semaphorin-7A. Reduction of semaphorin-7A induced increased proliferation and migration of non-fibrotic HLF. Also, independent of the presence of TGF-ß1, the decline of semaphorin-7A by siRNA was associated with increased α-smooth muscle actin production and gene expression of periostin, fibronectin, laminin, and serum response factor (SRF), indicating differentiation into a myofibroblast. Conversely, overexpression of semaphorin-7A in the NIH3T3 fibroblast cell line reduced the production of pro-fibrotic markers. The inverse association between semaphorin-7A and pro-fibrotic fibroblast markers was further analyzed using HLF from idiopathic pulmonary fibrosis (IPF) (n = 6) and non-fibrotic (n = 7) lungs. Using these 13 fibroblast lines, we observed that semaphorin-7A and periostin expression were inversely correlated. In conclusion, our study indicates that endogenous semaphorin-7A in HLF plays a role in maintaining fibroblast homeostasis by preventing up-regulation of pro-fibrotic genes. Therefore, endogenous and exogenous semaphorin-7A may have opposite effects on the fibroblast phenotype.Show less >

Language :

Anglais

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Autres travaux scientifiques

Submission date :

2023-10-23T15:09:00Z
2024-06-26T12:46:17Z