Histone deacetylase 7, a potential target for the antifibrotic treatment of systemic sclerosis

Area of Science:

• Molecular Biology
• Dermatology
• Fibrosis Research

Background:

• Systemic sclerosis (SSc) is characterized by excessive extracellular matrix deposition.
• Trichostatin A (TSA) reduces collagen and fibronectin transcription in SSc fibroblasts and prevents fibrosis in mouse models.
• The antifibrotic mechanism of TSA, particularly its effect on histone deacetylase 7 (HDAC-7), requires further investigation.

Purpose of the Study:

• To investigate the role of histone deacetylase 7 (HDAC-7) silencing as a mechanism for TSA's antifibrotic effects in systemic sclerosis (SSc).
• To compare the efficacy and specificity of HDAC-7 silencing with TSA treatment in SSc fibroblasts.

Main Methods:

• Systemic sclerosis (SSc) skin fibroblasts were treated with trichostatin A (TSA) and/or transforming growth factor beta.
• Expression of various histone deacetylases (HDACs), extracellular matrix proteins, CTGF, and ICAM-1 was analyzed using real-time PCR, Western blotting, and Sircol collagen assay.
• HDAC-7 was silenced using small interfering RNA (siRNA).

Main Results:

• TSA significantly inhibited HDAC-7 expression while up-regulating HDAC-3.
• Silencing HDAC-7 reduced type I and III collagen production but did not affect fibronectin levels.
• TSA increased CTGF and ICAM-1 expression, whereas HDAC-7 silencing had no impact on these molecules.

Conclusions:

• HDAC-7 silencing demonstrates efficacy comparable to TSA in reducing collagen production in SSc fibroblasts.
• Targeting HDAC-7 offers a more specific antifibrotic strategy for SSc, avoiding the upregulation of profibrotic molecules like ICAM-1 and CTGF.
• HDAC-7 silencing presents a promising avenue for developing targeted, less toxic therapies for systemic sclerosis.