Mechanical Strain Alters Gene Expression in an in Vitro Model of Hypertrophic Scarring

Derderian, Christopher A.; Bastidas, Nicholas; Lerman, Oren Z.; Bhatt, Kirit A.; Lin, Shin E.; Voss, Jeremy; Holmes, Jeffrey W.; Levine, Jamie P.; Gurtner, Geoffrey C.

doi:10.1097/01.sap.0000168160.86221.e9

Cited by 65 publications

(45 citation statements)

References 21 publications

(29 reference statements)

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“…3 More recent work has shown that fibroblast gene expression, including apoptosis signaling, matrix metalloproteinase (MMP) activity, and differentiation into myofibroblasts, are strongly linked to the rigidity or laxity of the ECM, even independent of transforming growth factor (TGF)-b signaling. [42][43][44][45][46][47][48] Even a 15% increase in cell stretch is capable of altering a fibroblast's orientation in relation to the ECM, inducing alterations in focal adhesion kinase signaling, or up-regulating expression of alpha smooth muscle actin (aSMA), consistent with differentiation into the contractile myofibroblast. 49,50 Some clinicians have theorized that reducing the tension on wound fibroblasts by paralyzing local muscle fibers may reduce myofibroblast proliferation and collagen production, thereby decreasing scarring.…”

Section: Collagen-mediated Mechanical Tensionmentioning

confidence: 99%

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

Tracy

Minasian

Caterson

2016

Advances in Wound Care

729

584

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Section: Collagen-mediated Mechanical Tensionmentioning

confidence: 99%

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

Tracy

Minasian

Caterson

2016

Advances in Wound Care

729

584

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“…Mechanical stimulation has been found in vitro to activate calcium mediated intracellular signaling in fibroblasts [17]. Human dermal fibroblasts have a linear increase in type I and III collagen and collagenase gene expression with increasing mechanical loads [18]. Human keloid fibroblasts increase transcription of TGFbeta 1 and 2 following mechanical strain when compared to normal fibroblasts [19].…”

Section: Tensionmentioning

confidence: 98%

Pathophysiology of post-operative scars

Qureshi

Orgill

2012

Eur Surg

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Background: Major surgical procedures result in varying degrees of scar as a visible endpoint of wound healing. Efforts to minimize post-operative scar formation that can lead to painful or unsightly scars have been motivated by the unpredictability and potential for abnormal scarring. The formation of scars following surgery is of particular interest to plastic surgeons. We review here the classic stages of wound repair and the mechanical forces that affect post-operative scarring.Methods: The peer-reviewed literature within the last 10 years was studied using an evidence-based approach.Results: Pre-clinical and clinical studies suggest that post-operative scar formation begins with the surgical incision and is influenced by the local wound environment as it passes through the classic stages of inflammation, proliferation and remodeling. Mechanical forces including tension, depth and epidermal closure all influence scarring as demonstrated in animal models and clinical experience. Dermal regeneration templates have both scar reductive and regenerative properties. Current scar therapy includes compression therapy, silicone gel sheeting, radiation therapy and molecular therapy albeit with variable success.Conclusions: Post-operative scar forms as the result of a highly conserved cascade of events following surgery that seeks to restore skin integrity and is influenced by the wound environment's physical properties likely through cellular mechanotransduction. While current therapies seek to minimize scar formation based on our understanding of these forces, further research on the molecular and mechanical forces affecting post-operative scarring will allow for clinical applications to minimization scar formation.

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“…The cornea is a dynamic tissue, capable of altering its ECM composition and biomechanical properties in response to changes in the visual environment (31,32). In addition, corneal fibroblasts have been demonstrated to respond actively to local tension changes in the ECM (33), and fibroblasts are a major type of mechanoresponsive cell (34). However, to date, there have been no reports regarding the effect of mechanical stretch on expression of MMP and TIMP in HKCFBs.…”

Section: Introductionmentioning

confidence: 96%

Induction of MMP-1 and −3 by cyclical mechanical stretch is mediated by IL-6 in cultured fibroblasts of keratoconus

Du¹,

Chen²,

Li³

et al. 2017

Molecular Medicine Reports

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Abstract. In order to understand the effect of mechanical stretch on corneal extracellular matrix remodeling, human keratoconus fibroblasts (HKCFBs) were subjected to cyclic stretch in vitro and the expression of matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and inflammatory cytokines were evaluated. HKCFBs were seeded into a flexible membrane base and subjected to a cyclic stretch regimen of 10% equibiaxial stretch at a stretching frequency of 1 Hz for 6 h using a Flexcell tension unit. An antibody directed against interleukin-6 (IL-6 Ab) was used to investigate the roles of IL-6 on mechanical stretch mediated regulation of MMP in HKCFBs. Culture supernatants were assayed using an enzyme-linked immunosorbent assay for MMP-1 and -3, TIMP-1 and -2, and IL-6. Total RNA from the cells was extracted, and quantitative polymerase chain reaction was used to determine mRNA for MMP-1 and -3, TIMP-1 and -2, and IL-6. In stretched cells, levels of MMP-1 and -3 demonstrated an increase compared with unstretched cells, but levels of TIMP-1, and -2 revealed a decrease. Mechanical stretch significantly increased the mRNA expression and protein synthesis of IL-6 compared with unstretched cells. IL-6 induced MMP-1 and -3 expression, whereas no significant effects were observed in levels of TIMP-1 and -2 compared with the untreated control groups. Additionally, the IL-6 Ab markedly inhibited the stretch-induced increase in MMP-1 and -3 in culture supernatants in a dose-dependent manner. No significant differences in TIMP-1 and -2 protein levels were detected between stretched cells treated with IL-6 Ab and stretched cells without IL-6 Ab treatment. These results indicate that cyclical mechanical stretch augments IL-6 production and MMP expression, and reduces levels of TIMP in HKCFBs. Thus, it is suggested that IL-6 mediates the stretch-induced MMP expression.

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Mechanical Strain Alters Gene Expression in an in Vitro Model of Hypertrophic Scarring

Cited by 65 publications

References 21 publications

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

Extracellular Matrix and Dermal Fibroblast Function in the Healing Wound

Pathophysiology of post-operative scars

Induction of MMP-1 and −3 by cyclical mechanical stretch is mediated by IL-6 in cultured fibroblasts of keratoconus

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