Tension enhances cell proliferation and collagen synthesis by upregulating expressions of integrin αvβ3 in human keloid-derived mesenchymal stem cells

Aims: Keloids are a dermal fibrotic disease whose etiology remains totally unknown and for which there is no successful treatment. Mechanical tension, in addition, is closely associated with the germination and development of keloids. In this study, we investigated the influence of human keloid-derived mesenchymal stem cells (KD-MSCs) on cell proliferation, collagen synthesis, and expressions of integrin alpha v beta 3 under tension. Main methods: KD-MSCs and human normal skin-derived mesenchymal stem cells (NS-MSCs) were isolated and cultured in stem cell medium with a gradual increase in the serum concentration. Cell proliferation and collagen synthesis were detected by Cell Counting Kit-8 (CCK-8) assay and hydroxyproline content analysis under tension respectively. We investigated the messenger RNA expressions of nine integrin subunits, including integrin units alpha 2, alpha 3, alpha 5, alpha v, alpha 8, alpha 10, alpha 11, beta 1, and beta 3, in KD-MSCs stimulated with tension. Identification of differentially expressed genes was performed by Western blot analysis and immunocytochemistry staining. Key findings: We obtained high-purity KD-MSCs and NS-MSCs using the culture method of decreasing serum concentration gradient gradually. Furthermore, we found that tension enhances cell proliferation and collagen synthesis and promotes expressions of integrin alpha v beta 3 in KD-MSCs. In addition, blocking experiments showed that increased integrin alpha v beta 3 expression affects cell proliferation and collagen synthesis of KD-MSCs under tension. Significance: Our results suggest that integrin alpha v beta 3 receptor may be sensitive molecules of mechanical tension and could contribute to the occurrence and development of keloids. It could lead to novel targets for therapeutic intervention, treatment, and prevention of recurrence for keloid disorders.