Haifeng Song1, Tao Liu1, Wenting Wang1, Hailin Pang2, Zhe Zhou3, Yajie Lv1, Tianyu Cao1, Da Zhai1, Bintao Ma1, Huizhong Zhang4, Yanguo Zhang5. 1. Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, No. 569 Xinsi Road, Xi'an 710038, Shaanxi, China. 2. Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, No. 569 Xinsi Road, Xi'an 710038, Shaanxi, China. 3. Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, No. 569 Xinsi Road, Xi'an 710038, Shaanxi, China; Department of Dermatology, Xi'an North Hospital, No. 170 Changle Middle Road, Xi'an 710043, Shaanxi, China. 4. Department of Clinical Laboratory, Tangdu Hospital, Fourth Military Medical University, No. 569 Xinsi Road, Xi'an 710038, Shaanxi, China. 5. Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, No. 569 Xinsi Road, Xi'an 710038, Shaanxi, China. Electronic address: Zhangya3341@163.com.
Abstract
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 αvβ3 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 α2, α3, α5, αv, α8, α10, α11, β1, and β3, 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 αvβ3 in KD-MSCs. In addition, blocking experiments showed that increased integrin αvβ3 expression affects cell proliferation and collagen synthesis of KD-MSCs under tension. SIGNIFICANCE: Our results suggest that integrin αvβ3 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.
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 αvβ3 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 α2, α3, α5, αv, α8, α10, α11, β1, and β3, 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 αvβ3 in KD-MSCs. In addition, blocking experiments showed that increased integrin αvβ3 expression affects cell proliferation and collagen synthesis of KD-MSCs under tension. SIGNIFICANCE: Our results suggest that integrin αvβ3 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.