Decorin, erythroblastic leukaemia viral oncogene homologue B4 and signal transducer and activator of transcription 3 regulation of semaphorin 3A in central nervous system scar tissue

Brain, 2011 · DOI: 10.1093/brain/awq304 · Published: April 1, 2011

Simple Explanation

Scar tissue in the central nervous system (CNS) after injury prevents axons from regenerating. Semaphorin 3A (Sema3A) is a growth inhibitor found in scar tissue. This study investigates how decorin, a proteoglycan, affects Sema3A expression after CNS injury. The study found that decorin reduces Sema3A expression in scar tissue and cultured leptomeningeal fibroblasts. This reduction depends on erythroblastic leukemia viral oncogene homologue B4 (ErbB4) and signal transducer and activator of transcription 3 (STAT3). These findings suggest decorin could be a potential therapy to promote axon growth and repair in the injured CNS by suppressing Sema3A and other inhibitory molecules.

Study Duration

8 days

Participants

Adult female Sprague Dawley rats (200–250 g)

Evidence Level

Not specified

Key Findings

1
Decorin infusion reduces Sema3A mRNA and protein levels in cerebral cortex scar tissue.
2
Decorin decreases Sema3A mRNA expression in cultured rat leptomeningeal fibroblasts.
3
Decorin-mediated Sema3A suppression depends on ErbB4 receptor activity and STAT3 signaling.

Research Summary

This study demonstrates that decorin core protein infusion suppresses Sema3A mRNA and protein levels in CNS injury sites, particularly in leptomeningeal fibroblasts within fibrotic scar tissue. Decorin's ability to suppress Sema3A expression is confirmed in cultured leptomeningeal fibroblasts and found to be dependent on ErbB4 receptor activity. The study also identifies a novel role for STAT3 signaling in regulating Sema3A expression and demonstrates that decorin induces the expression of STAT3 inhibitors, potentially suppressing Sema3A in injured CNS tissue.

Practical Implications

Therapeutic Potential

Decorin represents a potential therapeutic agent for promoting axon regeneration in the injured adult mammalian CNS.

Targeting Sema3A

Decorin treatment of CNS injuries is a complementary approach to other strategies designed to target the axon growth inhibitory effects of Sema3A.

Mechanism of Action

Understanding the mechanism by which decorin suppresses Sema3A expression may lead to new therapeutic targets for promoting CNS repair.

Study Limitations

1
The exact mechanism of cucurbitacin I inhibition on STAT3 signalling is presently unknown
2
The ligands and receptors promoting the expression of Sema3A by leptomeningeal ﬁbroblasts in either CNS injuries or in culture are currently unknown.
3
The ability of decorin to regulate the synthesis of Sema3A by neurons requires further investigation.

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