PURPOSE: Activation of transforming growth factor-β (TGF-β) signaling and matrix metalloproteinases are involved in hypertrophic scar (HS) formation. Compression therapy is known to be an effective approach for the treatment of hypertrophic scarring; however, the underlying molecular mechanisms remain poorly understood. We investigated the relationship between TGF-β signaling activation and matrix metalloproteinases in HS fibroblasts during mechanical compressive stress. MATERIALS AND METHODS: Two groups of skin tissue from HS and the nearby normal tissue were obtained from surgical patients and analyzed. Primary fibroblasts from the HS tissue and normal fibroblasts were isolated. Pressure therapy was recapitulated in an in vitro three-dimensional culture model, using mechanical stress produced with the Flexcell FX-4000C Compression Plus System. Quantitative real-time PCR (qPCR) was used to analyze the gene expression profiles in skin tissue and cultured primary cells exposed to compressive stress. Knockdown of SMAD2 and SMAD3 was performed using their specific siRNA in HS and normal fibroblasts subjected to compressive stress, and gene expression was examined by qPCR and Western blot. RESULTS: There was a significant upregulation of the mRNA expression of matrix metalloproteinase-2 (MMP2) and MMP9 in primary HS fibroblasts in response to mechanical stress. In contrast, the mRNA levels of collagen I and collagen III were downregulated in primary HS fibroblasts compared with those in the control cells. SiRNA-mediated knockdown of SMAD3 in the primary fibroblasts exposed to mechanical stress resulted in a decrease in the expression of MMP9 compared to control cells. CONCLUSION: These results demonstrate that compressive stress upregulates MMP9 by SMAD3 but not by SMAD2.
PURPOSE: Activation of transforming growth factor-β (TGF-β) signaling and matrix metalloproteinases are involved in hypertrophic scar (HS) formation. Compression therapy is known to be an effective approach for the treatment of hypertrophic scarring; however, the underlying molecular mechanisms remain poorly understood. We investigated the relationship between TGF-β signaling activation and matrix metalloproteinases in HS fibroblasts during mechanical compressive stress. MATERIALS AND METHODS: Two groups of skin tissue from HS and the nearby normal tissue were obtained from surgical patients and analyzed. Primary fibroblasts from the HS tissue and normal fibroblasts were isolated. Pressure therapy was recapitulated in an in vitro three-dimensional culture model, using mechanical stress produced with the Flexcell FX-4000C Compression Plus System. Quantitative real-time PCR (qPCR) was used to analyze the gene expression profiles in skin tissue and cultured primary cells exposed to compressive stress. Knockdown of SMAD2 and SMAD3 was performed using their specific siRNA in HS and normal fibroblasts subjected to compressive stress, and gene expression was examined by qPCR and Western blot. RESULTS: There was a significant upregulation of the mRNA expression of matrix metalloproteinase-2 (MMP2) and MMP9 in primary HS fibroblasts in response to mechanical stress. In contrast, the mRNA levels of collagen I and collagen III were downregulated in primary HS fibroblasts compared with those in the control cells. SiRNA-mediated knockdown of SMAD3 in the primary fibroblasts exposed to mechanical stress resulted in a decrease in the expression of MMP9 compared to control cells. CONCLUSION: These results demonstrate that compressive stress upregulates MMP9 by SMAD3 but not by SMAD2.
Authors: Danielle M DeBruler; Molly E Baumann; Jacob C Zbinden; Britani N Blackstone; John Kevin Bailey; Dorothy M Supp; Heather M Powell Journal: Adv Wound Care (New Rochelle) Date: 2020-06-02 Impact factor: 4.730
Authors: Niels A J Cremers; Maarten Suttorp; Marlous M Gerritsen; Ronald J Wong; Coby van Run-van Breda; Gooitzen M van Dam; Katrien M Brouwer; Anne Marie Kuijpers-Jagtman; Carine E L Carels; Ditte M S Lundvig; Frank A D T G Wagener Journal: Front Med (Lausanne) Date: 2015-12-15