Related Experiment Video
Updated: Mar 8, 2026
08:01
The Soft Agar Colony Formation Assay
Published on: October 27, 2014
114.1K
Endogenous Semaphorin-7A Impedes Human Lung Fibroblast Differentiation
Stephane Esnault1, Elizabeth E Torr1, Ksenija Bernau1
1Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, the University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, United States of America.
Plos One
|January 18, 2017
Summary
Endogenous semaphorin-7A maintains fibroblast homeostasis by suppressing pro-fibrotic gene expression in human lung fibroblasts. Its reduction promotes myofibroblast differentiation, while its overexpression has opposite effects.
Area of Science:
- Cell Biology
- Pulmonary Medicine
- Immunology
Background:
- Semaphorin-7A (SEMA7A) is a GPI-anchored protein involved in axon guidance and immune regulation.
- Exogenous SEMA7A can promote fibrosis, but its endogenous role in fibroblasts, particularly in pulmonary fibrosis, remains unclear.
- Previous studies in mouse models linked SEMA7A to TGF-ß1-induced pulmonary fibrosis, but not the specific function within fibroblasts.
Purpose of the Study:
- To investigate SEMA7A expression in primary human lung fibroblasts (HLF).
- To determine the functional role of endogenously expressed SEMA7A in HLF phenotype and pro-fibrotic gene expression.
- To analyze the association between SEMA7A and pro-fibrotic markers in fibroblasts from healthy and idiopathic pulmonary fibrosis (IPF) patients.
Main Methods:
- Quantification of SEMA7A expression in non-fibrotic HLF under varying serum and TGF-ß1 conditions.
- Utilized siRNA to reduce SEMA7A expression and assessed effects on proliferation, migration, and myofibroblast marker expression (α-SMA, periostin, fibronectin, laminin, SRF).
- Overexpressed SEMA7A in NIH3T3 fibroblasts to evaluate its impact on pro-fibrotic marker production.
- Correlated SEMA7A and periostin expression in HLF from IPF patients (n=6) and non-fibrotic controls (n=7).
Main Results:
- Non-fibrotic HLF expressed high levels of cell surface SEMA7A, independent of serum or TGF-ß1.
- siRNA-mediated reduction of SEMA7A increased HLF proliferation, migration, and induced myofibroblast differentiation (increased α-SMA, periostin, fibronectin, laminin, SRF).
- SEMA7A overexpression in NIH3T3 cells reduced pro-fibrotic markers.
- A significant inverse correlation was observed between SEMA7A and periostin expression in HLF from IPF patients and controls.
Conclusions:
- Endogenous SEMA7A in HLF acts as a crucial regulator of fibroblast homeostasis.
- SEMA7A prevents the upregulation of pro-fibrotic genes, thereby inhibiting myofibroblast differentiation.
- Endogenous and exogenous SEMA7A may exert opposing effects on the fibroblast phenotype, with implications for understanding pulmonary fibrosis pathogenesis.
