Skin equivalent tensional force alters keloid fibroblast behavior and phenotype

Area of Science:

• Biomedical Engineering
• Dermatology
• Cell Biology

Background:

• Skin tension is a known factor influencing keloid scar formation and progression.
• Understanding the cellular mechanisms underlying tension-induced keloid development is crucial for effective treatment strategies.

Purpose of the Study:

• To develop a 3D in vitro model that accurately mimics in vivo skin tension.
• To investigate the behavior of keloid fibroblasts (KF) and normal skin fibroblasts (NF) under mechanical tension.
• To analyze the impact of tension on extracellular matrix synthesis and tension-related gene expression in KFs and NFs.

Main Methods:

• Developed a 3D in vitro model using a fibroblast-populated collagen lattice subjected to physiologically relevant tension (35 mN).
• Measured the expression of tension-related genes (Hsp27, PAI-2, α2β1 integrin) and extracellular matrix genes in KFs and NFs over time (6, 12, 24 hours) with and without tension.
• Utilized gene knockdown techniques to assess the functional role of specific genes in fibroblast behavior and morphology.
• Quantified fibroblast proliferation and morphological changes under varying tension conditions.

Main Results:

• Keloid fibroblasts (KF) exhibited significantly higher proliferation and distinct gene expression patterns compared to normal skin fibroblasts (NF) under tension.
• Tension induced time-dependent regulation of Hsp27, PAI-2, and α2β1 integrin in both KF and NF, with differential responses observed between the two cell types.
• Down-regulation of these tension-related genes significantly altered extracellular matrix gene expression and fibroblast morphology, particularly in KFs.
• The 3D model successfully replicated in vivo forces and demonstrated significant differences in gene regulation and cell behavior between KFs and NFs.

Conclusions:

• Mechanical tension significantly influences keloid fibroblast behavior, including proliferation and gene expression, mediated by specific tension-related genes.
• The developed 3D in vitro model provides a valuable tool for studying mechano-regulation in keloid scar development.
• Targeting tension-induced pathways and genes holds potential for novel therapeutic strategies for keloid scars.