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      Vibrational stress affects extracellular signal-regulated kinases activation and cytoskeleton structure in human keratinocytes

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          Abstract

          As the outermost organ, the skin can be damaged following injuries such as wounds and bacterial or viral infections, and such damage should be rapidly restored to defend the body against physical, chemical, and microbial assaults. However, the wound healing process can be delayed or prolonged by health conditions, including diabetes mellitus, venous stasis disease, ischemia, and even stress. In this study, we developed a vibrational cell culture model and investigated the effects of mechanical vibrations on human keratinocytes. The HaCaT cells were exposed to vibrations at a frequency of 45 Hz with accelerations of 0.8g for 2 h per day. The applied mechanical vibration did not affect cell viability or cell proliferation. Cell migratory activity did increase following exposure to vibration, but the change was not statistically significant. The results of immunostaining (F-actin), western blot (ERK1/2), and RT-qPCR (FGF-2, PDGF-B, HB-EGF, TGF-β1, EGFR, and KGFR) analyses demonstrated that the applied vibration resulted in rearrangement of the cytoskeleton, leading to activation of ERK1/2, one of the MAPK signaling pathways, and upregulation of the gene expression levels of HB-EGF and EGFR. The results suggest that mechanical vibration may have wound healing potential and could be used as a mechanical energy-based treatment for enhancing wound healing efficiency.

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          Most cited references31

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          Molecular markers in patients with chronic wounds to guide surgical debridement.

          Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients' wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious.
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            Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing.

            Members of the epidermal growth factor (EGF) family are the most important growth factors involved in epithelialization during cutaneous wound healing. Heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family, is thought to play an important role in skin wound healing. To investigate the in vivo function of HB-EGF in skin wound healing, we generated keratinocyte-specific HB-EGF-deficient mice using Cre/loxP technology in combination with the keratin 5 promoter. Studies of wound healing revealed that wound closure was markedly impaired in keratinocyte-specific HB-EGF-deficient mice. HB-EGF mRNA was upregulated at the migrating epidermal edge, although cell growth was not altered. Of the members of the EGF family, HB-EGF mRNA expression was induced the most rapidly and dramatically as a result of scraping in vitro. Combined, these findings clearly demonstrate, for the first time, that HB-EGF is the predominant growth factor involved in epithelialization in skin wound healing in vivo and that it functions by accelerating keratinocyte migration, rather than proliferation.
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              Roles of the cytoskeleton, cell adhesion and rho signalling in mechanosensing and mechanotransduction.

              All cells sense and respond to various mechanical forces in and mechanical properties of their environment. To respond appropriately, cells must be able to sense the location, direction, strength and duration of these forces. Recent progress in mechanobiology has provided a better understanding of the mechanisms of mechanoresponses underlying many cellular and developmental processes. Various roles of mechanoresponses in development and tissue homeostasis have been elucidated, and many molecules involved in mechanotransduction have been identified. However, the whole picture of the functions and molecular mechanisms of mechanotransduction remains to be understood. Recently, novel mechanisms for sensing and transducing mechanical stresses via the cytoskeleton, cell-substrate and cell-cell adhesions and related proteins have been identified. In this review, we outline the roles of the cytoskeleton, cell-substrate and cell-cell adhesions, and related proteins in mechanosensing and mechanotransduction. We also describe the roles and regulation of Rho-family GTPases in mechanoresponses.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                8 April 2020
                2020
                : 15
                : 4
                : e0231174
                Affiliations
                [1 ] Department of Biological Engineering, Inha University, Incheon, Korea
                [2 ] Biology and Medical Device Evaluation Team, Korea Testing & Research Institute, Gwacheon, Korea
                Dongguk University, REPUBLIC OF KOREA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-3698-9346
                http://orcid.org/0000-0002-5324-2711
                Article
                PONE-D-19-35448
                10.1371/journal.pone.0231174
                7141684
                32267880
                c071ae6e-3d06-4763-ac4e-16a21e94101a
                © 2020 Kim, Kwon

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 December 2019
                : 17 March 2020
                Page count
                Figures: 8, Tables: 2, Pages: 17
                Funding
                Funded by: National Rsearch Foundation of Korea
                Award ID: NRF-2017R1D1A1B03029589
                Award Recipient :
                Funded by: Inha University Research Grant
                Award ID: 61529-01
                Award Recipient :
                This study was supported by the National Research Foundation of Korea (NRF-2017R1D1A1B03029589) and an Inha University Research Grant, Korea (61529-01) to SK.
                Categories
                Research Article
                Physical Sciences
                Physics
                Classical Mechanics
                Vibration
                Biology and Life Sciences
                Physiology
                Physiological Processes
                Tissue Repair
                Wound Healing
                Medicine and Health Sciences
                Physiology
                Physiological Processes
                Tissue Repair
                Wound Healing
                Biology and Life Sciences
                Cell Biology
                Cell Processes
                Cell Proliferation
                Engineering and Technology
                Mechanical Engineering
                Vibration Engineering
                Biology and Life Sciences
                Genetics
                Gene Expression
                Biology and Life Sciences
                Cell Biology
                Cellular Structures and Organelles
                Cytoskeleton
                Biology and Life Sciences
                Cell Biology
                Cell Motility
                Cell Migration
                Biology and Life Sciences
                Developmental Biology
                Cell Migration
                Medicine and Health Sciences
                Endocrinology
                Endocrine Physiology
                Growth Factors
                Biology and Life Sciences
                Physiology
                Endocrine Physiology
                Growth Factors
                Medicine and Health Sciences
                Physiology
                Endocrine Physiology
                Growth Factors
                Custom metadata
                All relevant data are within the manuscript and its Supporting Information files.

                Uncategorized
                Uncategorized

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