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Journal ArticleDOI

Extracorporeal Shock Wave Therapy Alters the Expression of Fibrosis-Related Molecules in Fibroblast Derived from Human Hypertrophic Scar.

02 Jan 2018-International Journal of Molecular Sciences (Multidisciplinary Digital Publishing Institute)-Vol. 19, Iss: 1, pp 124
TL;DR: In this article, the authors investigated the mechanism underlying changes in cellular and molecular biology induced by extracorporeal shock wave therapy of fibroblasts derived from scar tissue (HTSFs), and found that suppressed epithelial-mesenchymal transition might be responsible for the anti-scarring effect of ESWT.
Abstract: Extracorporeal shock wave therapy (ESWT) considerably improves the appearance and symptoms of post-burn hypertrophic scars (HTS). However, the mechanism underlying the observed beneficial effects is not well understood. The objective of this study was to elucidate the mechanism underlying changes in cellular and molecular biology that is induced by ESWT of fibroblasts derived from scar tissue (HTSFs). We cultured primary dermal fibroblasts derived from human HTS and exposed these cells to 1000 impulses of 0.03, 0.1, and 0.3 mJ/mm². At 24 h and 72 h after treatment, real-time PCR and western blotting were used to detect mRNA and protein expression, respectively, and cell viability and mobility were assessed. While HTSF viability was not affected, migration was decreased by ESWT. Transforming growth factor beta 1 (TGF-β1) expression was reduced and alpha smooth muscle actin (α-SMA), collagen-I, fibronectin, and twist-1 were reduced significantly after ESWT. Expression of E-cadherin was increased, while that of N-cadherin was reduced. Expression of inhibitor of DNA binding 1 and 2 was increased. In conclusion, suppressed epithelial-mesenchymal transition might be responsible for the anti-scarring effect of ESWT, and has potential as a therapeutic target in the management of post-burn scars.
Citations
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Journal ArticleDOI
TL;DR: Li-ESWT for ED, based on current experimental studies, seems to improve erectile function by inducing angiogenesis and reversing pathologic processes in erectile tissue.

47 citations

Journal ArticleDOI
TL;DR: Clinically, post-burn pruritus tends to be intractable to conventional treatment but rather responds to neuroleptic agents, such as gabapentin and pregabalin.
Abstract: Post-burn pruritus is the pruritus that occurs after burn during the rehabilitation and healing process of burn wounds. The post-burn pruritus is a common and serious complication of burn injury, which severely lowers the quality of life of the patient. Many potential treatments are available for pruritus but there is no consensus of the best single treatment yet. The precise mechanism of post-burn pruritus has not been elucidated, but it appears to have pruritogenic and neuropathic aspects. Clinically, post-burn pruritus tends to be intractable to conventional treatment but rather responds to neuroleptic agents, such as gabapentin and pregabalin. During wound healing, various neuropeptides secreted from the nerves of the skin control epidermal and vascular proliferation and connective tissue cells. When keratinocytes are activated by an itch-inducing substance, they secrete a variety of inflammatory substances that increase the susceptibility of the itch receptor. There are two mechanisms underlying post-burn neuropathic pruritus. The first one is peripheral sensitization. The second one is the intact nociceptor hypothesis. An effective treatment for post-burn pruritus will also be effective in other neuropathic and intractable itching. In this review, we summarized the interaction and mechanism of keratinocytes, immune cells, and nerve fibers related to post-burn pruritus.

31 citations


Cites background from "Extracorporeal Shock Wave Therapy A..."

  • ...Even an interaction with the numerous cytokines as well as with CGRP appears feasible [78,79]....

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Journal ArticleDOI
TL;DR: The progress in the molecular mechanism of HSs is summarized, the available biotherapeutic methods for their pathophysiological characteristics are reviewed, and it is prospected that the comprehensive therapy may be more suitable for HS treatment.
Abstract: Scar formation is usually the pathological consequence of skin trauma. And hypertrophic scars (HSs) frequently occur in people after being injured deeply. HSs are unusually considered as the result of tissue contraction and excessive extracellular matrix component deposition. Myofibroblasts, as the effector cells, mainly differentiated from fibroblasts, play the crucial role in the pathophysiology of HSs. A number of growth factors, inflammatory cytokines involved in the process of HS occurrence. Currently, with in-depth exploration and clinical research of HSs, various creative and effective treatments budded. In here, we summarize the progress in the molecular mechanism of HSs, and review the available biotherapeutic methods for their pathophysiological characteristics. Additionally, we further prospected that the comprehensive therapy may be more suitable for HS treatment.

21 citations


Cites background from "Extracorporeal Shock Wave Therapy A..."

  • ...It was shown that extracorporeal shock wave therapy was responsible for the anti-scarring by suppressing EMT in the post-burn scars.(125) As such, focus on the dysregulation of injury-triggered EMT is proved to contribute to HSs treatment....

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Journal Article
TL;DR: This study provides evidence that excessive scarring is associated with a failure to eliminate TGF β receptor overexpressing fibroblasts during granulation tissue remodeling, which leads to a persistent autocrine, positive feedback loop that results in over production of matrix proteins and subsequent fibrosis.
Abstract: In the present study we have analyzed and compared,by immunohistochemistry and in situ hybridization,the expression pattern of the R4/ALK5 transforming growth factor (TGF) β type Ⅰ receptor(RI) and the TGF β type Ⅱ receptor(RII) in normal human skin,in wounded skin at various stages during the transition of wound granulation tissue to scar,and in longpersisting post burn hypertrophic scars. In normal human skin,expression of RI and RII was clearly visible in the epidermis,in epidermal appendages,and in vascular cells,although only a small number of dermal fibroblasts revealed detectable levels of TGF β receptor expression. In contrast,granulation tissue fibroblasts showed strong expression of both TGF β receptor types, although in normal healing excisional wounds their density decreased during granulation tissue remodeling. However,in post burn hypertrophic scars,RI and RII overexpressing fibroblasts were found in high densities up to 20 months after injury. From these findings we suggest that the repair process of deep wounds involves the transformation of a subset of fibroblastic cells toward an increased TGF β responsiveness and a transient accumulation of these cells at the wound site. In addition,our study provides evidence that excessive scarring is associated with a failure to eliminate TGF β receptor overexpressing fibroblasts during granulation tissue remodeling,which leads to a persistent autocrine,positive feedback loop that results in over production of matrix proteins and subsequent fibrosis.

20 citations

Journal ArticleDOI
Rei Ogawa1
TL;DR: The purpose of the Special Issue “Recent Advances in Scar Biology” that was published recently in the International Journal of Molecular Sciences was to illustrate the biological mechanisms that underpin scarring and effective clinical treatments.
Abstract: Scars develop in the final stage of wound healing. The biological pathways that underlie wound healing and scarring are complex. In particular, the exact mechanisms that initiate and regulate them and lead to their progression remain to be fully elucidated. A major goal of medical science is scar-less wound healing. To achieve this goal, it is necessary to elucidate the relevant clinical, histopathological, and molecular manifestations of scars, and to understand how these manifestations relate to each other. The purpose of the Special Issue “Recent Advances in Scar Biology” that was published recently in the International Journal of Molecular Sciences was to illustrate the biological mechanisms that underpin scarring and effective clinical treatments. This Special Issue included a selection of recent research topics and current review articles in the field of scar research for all kinds of tissues and organs. Normally, the cutaneous wound healing process closes skin gaps by inducing the formation of granulation tissue and epithelialization, which re-establishes an effective epidermal barrier. The complex biochemical events that underlie wound closure can be categorized into four overlapping processes: coagulation, inflammation, proliferation and remodeling. Coagulation and the inflammatory process begin immediately after injury, while the proliferative phases start within a few days. The remodeling phase commences within a week of injury and continues for months. If the inflammatory and proliferative phases are feeble, wound healing may be delayed and chronic wounds may develop. In relation to this, Horng et al. [1] showed in the Special Issue that estrogen deficiency, such as that in postmenopausal women, has detrimental effects on wound-healing processes, particularly inflammation and re-granulation, and that exogenous estrogen treatment may reverse these effects [1]. Conversely, if the inflammatory and proliferative phases are excessively vigorous and prolonged due, for example, to infection or burn, heavy scars can develop. Clinical interventions that target these phases can, therefore, improve wound healing. For example, Jeong et al. [2] showed in a rat incisional wound-healing model that injections with polydeoxyribonucleotide (a mixture of nucleotides from trout sperm) have anti-inflammatory effects and, therefore, reduce the size of the scar [2]. After full-thickness burning, necrotized tissues (eschars) develop. These eschars delay wound healing, thereby promoting the formation of hypertrophic scars. Monsuur et al. [3] showed in the Special Issue that, while acellular extracts of burn eschars stimulate the proliferation and migration of adipose mesenchymal stromal cells and fibroblasts, they also inhibit the basic fibroblast growth factor-induced proliferation and sprouting of endothelial cells. This inhibitory effect may explain why the presence of an eschar blocks the formation of excessive granulation tissue by full-thickness burn wounds [3]. Akita et al. also showed that proper epithelialization plays an important role in the healing of burn wounds: when patients with extensive burns received cultured epithelial autografts (CEA) along with either highly expanded (over 1:6 ratio) or less expanded (gap 1:6) mesh, the former combination was associated with accelerated wound healing. Moreover, scoring by experts using the Vancouver and Manchester Scar Scales showed that CEA with the highly expanded mesh led to better scar formation [4]. The exhaustive review of Mostaço-Guidolin et al. also showed that proper formation of the extracellular matrix plays a key role in the epithelialization and other wound-healing events that lead to a smooth wound-healing course: studies that used second harmonic generation

17 citations

References
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Journal ArticleDOI
01 Dec 2001-Methods
TL;DR: The 2-Delta Delta C(T) method as mentioned in this paper was proposed to analyze the relative changes in gene expression from real-time quantitative PCR experiments, and it has been shown to be useful in the analysis of realtime, quantitative PCR data.

139,407 citations

Journal ArticleDOI
TL;DR: This review highlights recent advances in the process of EMT signaling in health and disease and how it may be attenuated or reversed by selective cytokines and growth factors.
Abstract: Epithelial to mesenchymal transition (EMT) is a central mechanism for diversifying the cells found in complex tissues. This dynamic process helps organize the formation of the body plan, and while EMT is well studied in the context of embryonic development, it also plays a role in the genesis of fibroblasts during organ fibrosis in adult tissues. Emerging evidence from studies of renal fibrosis suggests that more than a third of all disease-related fibroblasts originate from tubular epithelia at the site of injury. This review highlights recent advances in the process of EMT signaling in health and disease and how it may be attenuated or reversed by selective cytokines and growth factors.

2,426 citations


"Extracorporeal Shock Wave Therapy A..." refers background in this paper

  • ...EMT is a process by which epithelial cells lose their epithelial cell characteristics and develop properties typical of mesenchymal cells [26]....

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Journal ArticleDOI
06 Apr 1990-Cell
TL;DR: It is proposed that HLH proteins lacking a basic region may negatively regulate other HLHprotein through the formation of nonfunctional heterodimeric complexes.

2,203 citations


"Extracorporeal Shock Wave Therapy A..." refers background in this paper

  • ...The ID protein family has four family members (ID1-4), which can bind to basic helix–loop–helix (bHLH) transcription factors to form a heterodimer that inhibits transcription factor–DNA binding [40,41]....

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  • ...ID proteins can interact with Myo D protein, which is a myogenic bHLH transcription factor, to negatively regulate myogenic differentiation [40]....

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Journal ArticleDOI
TL;DR: It is believed that context and various changes in plasticity biomarkers can help identify at least three types of EMT and that using a collection of criteria for EMT increases the likelihood that everyone is studying the same phenomenon - namely, the transition of epithelial and endothelial cells to a motile phenotype.
Abstract: In the early 19th century, building on observations of microscopists now ancient, Schleiden and Schwann formulated the doctrine that cells are building blocks for plant and animal tissues (1). By the mid-19th century, Raspail, Remak, and Virchow expanded this hypothesis by suggesting that all cells come from preexisting cells — the so-called cell theory. Although referring to cell division, this now classic notion is prescient of another contemporary twist in the biology of cell maturation: beyond lineage development and normal differentiation, mature epithelial cells under new environmental pressures exhibit a local plasticity that allows them to morph into other mature phenotypes with or without proliferation (2, 3). Growing interest in the biology of these cellular transitions helped both establish epithelial cell plasticity as a field of study in the late 20th century and fashion much of the current thinking regarding morphogenesis in early embryonic development, tissue repair, and cancer metastasis (4–6). The details of some of these processes are not discussed here, as they are outlined in other articles in this Review Series on epithelial-mesenchymal transition (EMT) (7, 8). Instead, we offer a personal view gathered from our own experience and the literature regarding an approach documenting EMT events in culture or tissue. We hope this serves to stimulate other points of view as new data emerge.

2,016 citations


"Extracorporeal Shock Wave Therapy A..." refers background in this paper

  • ...In particular, expression levels of N- and E-cadherin are closely involved in EMT [36], where the loss of E-cadherin is correlated with an upregulation of N-cadherin [37]....

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Journal ArticleDOI
TL;DR: In this article, the immunological mechanisms that initiate, sustain and suppress the fibrotic process were studied. But the mechanisms that are involved in fibrogenesis are now known to be distinct from those involved in inflammation.
Abstract: Tissue fibrosis (scarring) is a leading cause of morbidity and mortality. Current treatments for fibrotic disorders, such as idiopathic pulmonary fibrosis, hepatic fibrosis and systemic sclerosis, target the inflammatory cascade, but they have been widely unsuccessful, largely because the mechanisms that are involved in fibrogenesis are now known to be distinct from those involved in inflammation. Several experimental models have recently been developed to dissect the molecular mechanisms of wound healing and fibrosis. It is hoped that by better understanding the immunological mechanisms that initiate, sustain and suppress the fibrotic process, we will achieve the elusive goal of targeted and effective therapeutics for fibroproliferative diseases.

1,466 citations