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Journal ArticleDOI

Normal skin and hypertrophic scar fibroblasts differentially regulate collagen and fibronectin expression as well as mitochondrial membrane potential in response to basic fibroblast growth factor.

01 Apr 2011-Brazilian Journal of Medical and Biological Research (Braz J Med Biol Res)-Vol. 44, Iss: 5, pp 402-410

TL;DR: BFGF has differential effects and mechanisms on fibroblasts of the normal skin and hypertrophic scars, indicating that bFGF may play a role in the early phase of skin wound healing and post-burn scar formation.

AbstractBasic fibroblast growth factor (bFGF) regulates skin wound healing; however, the underlying mechanism remains to be defined. In the present study, we determined the effects of bFGF on the regulation of cell growth as well as collagen and fibronectin expression in fibroblasts from normal human skin and from hypertrophic scars. We then explored the involvement of mitochondria in mediating bFGF-induced effects on the fibroblasts. We isolated and cultivated normal and hypertrophic scar fibroblasts from tissue biopsies of patients who underwent plastic surgery for repairing hypertrophic scars. The fibroblasts were then treated with different concentrations of bFGF (ranging from 0.1 to 1000 ng/mL). The growth of hypertrophic scar fibroblasts became slower with selective inhibition of type I collagen production after exposure to bFGF. However, type III collagen expression was affected in both normal and hypertrophic scar fibroblasts. Moreover, fibronectin expression in the normal fibroblasts was up-regulated after bFGF treatment. bFGF (1000 ng/mL) also induced mitochondrial depolarization in hypertrophic scar fibroblasts (P < 0.01). The cellular ATP level decreased in hypertrophic scar fibroblasts (P < 0.05), while it increased in the normal fibroblasts following treatment with bFGF (P < 0.01). These data suggest that bFGF has differential effects and mechanisms on fibroblasts of the normal skin and hypertrophic scars, indicating that bFGF may play a role in the early phase of skin wound healing and post-burn scar formation.

Topics: Hypertrophic scar (63%), Wound healing (58%), Basic fibroblast growth factor (57%), Fibronectin (56%), Type I collagen (56%)

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Citations
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Journal ArticleDOI
TL;DR: The therapeutic implications and future challenges of these molecular discoveries are critically discussed in the hope of advancing therapeutic approaches to limit pathological scar formation.
Abstract: Hypertrophic scars represent the most common complication of skin injury and are caused by excessive cutaneous wound healing characterized by hypervascularity and pathological deposition of extracellular matrix (ECM) components. To date, the optimal and specific treatment methods for hypertrophic scars have not been available in the clinic. Current paradigm has established fibroblasts and myofibroblasts as pivotal effector cells in the pathophysiology of wound healing. Their biological properties including origin, proliferation, migration, contraction and ECM regulation have profound impacts on the progression and regression of hypertrophic scars. These complex processes are executed and modulated by a signaling network involving a number of growth factors and cytokines. Of particular importance is transforming growth factor-β, platelet-derived growth factor, connective tissue growth factor, epidermal growth factor, and vascular endothelial growth factor. This review article briefly describes the biological functions of fibroblasts and myofibroblasts during hypertrophic scars, and thereafter examines the up-to-date molecular knowledge on the roles of key growth factor pathways in the pathophysiology of hypertrophic scars. Importantly, the therapeutic implications and future challenges of these molecular discoveries are critically discussed in the hope of advancing therapeutic approaches to limit pathological scar formation.

55 citations


Journal ArticleDOI
TL;DR: The clinical presentation of aberrant scars is reviewed and it is illustrated how they can be differentiated and how altered expression levels and the distribution of several factors may contribute to their unique clinical characteristics and presentation.
Abstract: GENERAL PURPOSE:To provide information about the clinical presentation of hypertrophic scars and keloids based on their varied structural components.TARGET AUDIENCE:This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest i

40 citations


Cites background from "Normal skin and hypertrophic scar f..."

  • ...Perhaps not surprisingly, the proliferative capacity of fibroblasts from hypertrophic scars is greater than that of normal skin.(24) However, compared with normal skin and hypertrophic scars, keloid fibroblasts possess higher proliferating cell nuclear antigen expression and display apoptosis resistance....

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Journal ArticleDOI
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.

28 citations


Cites background from "Normal skin and hypertrophic scar f..."

  • ...For example, HTSFs reportedly have a myofibroblast-like character [27]; high levels of TGF-β1 and its receptors; elevated expression of growth factors and inflammatory cytokines, such as CTGF, IL-6, and IL-8; and, Figure 7....

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  • ...HTSFs reportedly have a myofibroblast-like character [27]; high levels of TGF-β1 and its receptors; elevated expression of growth factors and inflammatory cytokines, such as CTGF, IL-6, and IL-8; and, increased ECM components as fibronectin and collagen [28]....

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Journal ArticleDOI
TL;DR: This study demonstrated that both peptide composition and MW distribution play important roles in anti-inflammatory activity, indicating the responsible role of low-MW bioactive peptides in exerting the beneficial biological function.
Abstract: Ovomucin is a mucin-like protein from egg white with a variety of biological functions. We hypothesized that ovomucin-derived peptides might exert anti-inflammatory activity. The specific objectives were to test the anti-inflammatory activities of different ovomucin hydrolysates and its various fractions in human dermal fibroblasts, and to understand the possible molecular mechanisms. Three ovomucin hydrolysates were prepared and desalted; only the desalted Alcalase hydrolysate showed anti-inflammatory activity. Desalting of ovomucin hydrolysate enriched the proportion of low-molecular-weight (MW) peptides. Indeed, ultrafiltration of this hydrolysate displayed comparable anti-inflammatory activity in dermal fibroblasts, indicating the responsible role of low-MW bioactive peptides in exerting the beneficial biological function. The anti-inflammatory activity of low-MW peptides was regulated through the inhibition of tumor necrosis factor-mediated nuclear factor κ-light-chain-enhancer of activated B cells activity. Our study demonstrated that both peptide composition and MW distribution play important roles in anti-inflammatory activity. The low-MW fractions prepared from ovomucin Alcalase hydrolysate may have potential applications for maintenance of dermal health and treatment of skin diseases.

28 citations


Journal ArticleDOI
Zhengzheng Wu1, Lina Fan, Bin Xu, Yongliang Lin, Peng Zhang, Xing Wei 
TL;DR: Xenogeneic decellularized scaffold was prepared with pig peritoneum by a series of biochemical treatments to retain normal three-dimensional tissue scaffold and remove cells and antigenic components from the tissue and can be further tested for skin tissue engineering.
Abstract: Skin damage is one of the common clinical skin diseases, and the main cure is the use of skin graft, especially for large area of skin injury or deep-skin damage. However, skin graft demand is far greater than that currently available. In this study, xenogeneic decellularized scaffold was prepared with pig peritoneum by a series of biochemical treatments to retain normal three-dimensional tissue scaffold and remove cells and antigenic components from the tissue. Scaffold was combined with hyaluronic acid (HA) plus two different concentrations of basic fibroblast growth factor (bFGF) and tested for its use for the repair of skin wounds. HA enhanced bFGF to adsorb to the decellularized scaffolds and slowed the release of bFGF from the scaffolds in vitro. A total of 20 rabbits were sacrificed on day 3, 6, 11, or 14 postsurgery. The wound healing rate and the thickness of dermis layer of each wound were determined for analyzing the wound repair. Statistical analysis was performed by the two-tailed Student's t...

24 citations


References
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Journal ArticleDOI
TL;DR: The primary goals of the treatment of wounds are rapid wound closure and a functional and aesthetically satisfactory scar.
Abstract: The primary function of the skin is to serve as a protective barrier against the environment. Loss of the integrity of large portions of the skin as a result of injury or illness may lead to major disability or even death. Every year in the United States more than 1.25 million people have burns1 and 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or diabetes mellitus.2 The primary goals of the treatment of wounds are rapid wound closure and a functional and aesthetically satisfactory scar. Recent advances in cellular and molecular biology have greatly expanded our understanding . . .

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"Normal skin and hypertrophic scar f..." refers background in this paper

  • ...PR OV IS IO NA L myofibroblasts disappear from the scar (2)....

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Journal ArticleDOI
TL;DR: Once MMP has been induced, it causes the release of catabolic hydrolases and activators of such enzymes (including those of caspases) from mitochondria, meaning that mitochondria coordinate the late stage of cellular demise.
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  • ...It has been previously demonstrated that mitochondrial permeability transition causes ΔΨm dissipation, uncoupling of oxidative phosphorylation, ATP depletion, and equilibration of small solutes and ions between the cytosol and the mitochondrial matrix to control cell death or survival (31)....

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Journal ArticleDOI
TL;DR: This review summarizes the results of expression studies that have been performed in rodents, pigs, and humans to localize growth factors and their receptors in skin wounds and reports on genetic studies addressing the functions of endogenous growth factors in the wound repair process.
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2,939 citations


"Normal skin and hypertrophic scar f..." refers background in this paper

  • ...Fibroblasts play an important role in wound healing by producing a provisional wound healing matrix, including collagen and fibronectin (1)....

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Journal ArticleDOI
TL;DR: Current understanding of the cellular and molecular mechanisms of fibrogenesis is explored and components of the renin–angiotensin–aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs.
Abstract: Fibrosis is defined by the overgrowth, hardening, and/or scarring of various tissues and is attributed to excess deposition of extracellular matrix components including collagen. Fibrosis is the end result of chronic inflammatory reactions induced by a variety of stimuli including persistent infections, autoimmune reactions, allergic responses, chemical insults, radiation, and tissue injury. Although current treatments for fibrotic diseases such as idiopathic pulmonary fibrosis, liver cirrhosis, systemic sclerosis, progressive kidney disease, and cardiovascular fibrosis typically target the inflammatory response, there is accumulating evidence that the mechanisms driving fibrogenesis are distinct from those regulating inflammation. In fact, some studies have suggested that ongoing inflammation is needed to reverse established and progressive fibrosis. The key cellular mediator of fibrosis is the myofibroblast, which when activated serves as the primary collagen-producing cell. Myofibroblasts are generated from a variety of sources including resident mesenchymal cells, epithelial and endothelial cells in processes termed epithelial/endothelial-mesenchymal (EMT/EndMT) transition, as well as from circulating fibroblast-like cells called fibrocytes that are derived from bone-marrow stem cells. Myofibroblasts are activated by a variety of mechanisms, including paracrine signals derived from lymphocytes and macrophages, autocrine factors secreted by myofibroblasts, and pathogen-associated molecular patterns (PAMPS) produced by pathogenic organisms that interact with pattern recognition receptors (i.e. TLRs) on fibroblasts. Cytokines (IL-13, IL-21, TGF-beta1), chemokines (MCP-1, MIP-1beta), angiogenic factors (VEGF), growth factors (PDGF), peroxisome proliferator-activated receptors (PPARs), acute phase proteins (SAP), caspases, and components of the renin-angiotensin-aldosterone system (ANG II) have been identified as important regulators of fibrosis and are being investigated as potential targets of antifibrotic drugs. This review explores our current understanding of the cellular and molecular mechanisms of fibrogenesis.

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Journal Article

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"Normal skin and hypertrophic scar f..." refers background in this paper

  • ..., transforming growth factor ß1 (TGF-ß1), insulin-like growth factor 1 (IGF-1), and interleukin-1] and exaggerated responses to these cytokines may also play a role in post-burn scars such as fibrosis and keloids (3)....

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  • ...Excessive myofibroblast differentiation and extracellular matrix formation may be involved in hypertrophic scarring and formation of post-burn scars, such as fibrosis and keloids (3), resulting in hypertrophic scars, the management of which remains a challenge in clinical practice....

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  • ...However, in pathological situations such as hypertrophic scar (HS), myofibroblasts persist in the tissue (3)....

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