Ascorbic acid promotes a TGFβ1-induced myofibroblast phenotype switch.

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• l-Ascorbic acid (vitamin C) is essential for collagen maturation.
• Its role in myofibroblast phenotype regulation beyond collagen synthesis is not fully understood.

Purpose of the Study:

• To investigate additional functions of ascorbic acid in regulating myofibroblast phenotype.
• To explore vitamin C's impact on myofibroblast characteristics beyond collagen biosynthesis.

Main Methods:

• Assessed TGFβ1-induced gene expression (COL1A1, ACTA2, COL4A1, DDR1, CCN2).
• Evaluated αSMA stress fiber formation and collagen synthesis/deposition.
• Measured myofibroblast contraction in a 3D collagen lattice.
• Investigated the role of Smad2/3 signaling.

Main Results:

• Ascorbic acid positively influenced TGFβ1-induced expression of COL1A1, ACTA2, and COL4A1.
• AA promoted αSMA stress fiber formation and collagen type I and IV synthesis/deposition.
• AA amplified myofibroblast contractile phenotype and increased DDR1 and CCN2 expression.
• The mechanism of AA action appeared independent of Smad2/3 signaling.

Conclusions:

• Ascorbic acid plays a significant role in regulating myofibroblast phenotype and function.
• Vitamin C enhances myofibroblast contractility and gene expression, suggesting broader biological roles.
• AA's effects on myofibroblasts are mediated through pathways independent of Smad2/3 signaling.