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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.
Abstract: Basic 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.

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Citations
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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

69 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
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.

67 citations

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.

43 citations

Journal ArticleDOI
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.

42 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: It is found that the use of two rather than one enzyme for hydrolysis generates a greater abundance of low molecular weight peptides with consequent improvement in bioactive properties.

42 citations

References
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Journal ArticleDOI
TL;DR: Two studies explored a new method for simultaneously inhibiting MC proliferation and ECM accumulation, which may represent a novel therapeutic approach to glomerulosclerosis.
Abstract: Extracellular matrix (ECM) expansion and mesangial cell (MC) proliferation are prominent features of most types of glomerulosclerosis. A delicate balance between the ECM and MC regulates cell survival. Increasing evidence shows that a loss of ECM components can cause mitochondrial dysfunction and induce cell apoptosis. It is proposed that directly blocking the synthesis of ECM components could lighten ECM accumulation and suppress cell overproliferation status. Fibronectin, one of the predominant adhesive glycoproteins of the mesangial ECM, provides the survival signal for cells. Its accumulation can be observed in most types of glomerulosclerosis. In this study, angiotensin II-induced fibronectin was suppressed by an RNA interference technique. It is interesting that MC slowly underwent apoptosis after infection with a retrovirus that continuously suppressed fibronectin synthesis. It was found that MC apoptosis occurred in a mitochondria-dependent manner mainly as a result of cytochrome c release and downstream caspase-3 and -9 activation. Furthermore, it was demonstrated that fibronectin knockdown affected mitochondrial handling of Ca 2+ release from the endoplasmic reticulum. Importantly, blocking the inositol 1,4,5-triphosphate receptor with, 3,4,5-trimethoxybenzoate or decreasing Ca 2+ in the ECM with EGTA partially saved the cells from apoptosis. These studies, which explored a new method for simultaneously inhibiting MC proliferation and ECM accumulation, may represent a novel therapeutic approach to glomerulosclerosis.

33 citations


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

  • ...In addition, mitochondria may be an important mediator in extracellular matrix homeostasis and cell proliferation (11-13)....

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Journal ArticleDOI
TL;DR: Investigation of whether topical application of plasma Fn improves healing of full-thickness skin wounds in rats found a significantly higher wound closure rate and hydroxyproline level in the skin than the control group and histologic analysis of macrophage and fibroblast migration, collagen regeneration, and epithelialization were significantly increased.
Abstract: Fibronectin (Fn) has been shown to play an important role in wound healing because it appears to be the stimulus for migration of fibroblasts and epidermal cells. The purpose of this study was to investigate whether topical application of plasma Fn (pFn) improves healing of full-thickness skin wounds in rats. A round section of full-thickness skin (diameter of approximately 15 mm) was resected in rats. Animals were then divided into two groups, and wounds were treated topically with a single application of human plasma albumin (control group) or human pFn (FN group). Wound closure rate, hydroxyproline concentration, and histologic features (immunohistochemical staining) were evaluated. The FN group had a significantly higher wound closure rate and hydroxyproline level in the skin than the control group. Histologic analysis of macrophage and fibroblast migration, collagen regeneration, and epithelialization were significantly increased in the FN group compared with the control group. A single topical application of pFn increased the migration of macrophages, myofibroblasts, and fibroblasts. Moreover, further release of transforming growth factor-beta1 from activated fibroblasts, keratinocytes, and epithelial cells may also contribute to the beneficial effect of pFn on wound healing.

28 citations


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

  • ...Fibronectin is also highly up-regulated after wound healing and acts as a provisional matrix, promoting fibroblast migration in the early phase of wound healing (28,29)....

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Journal ArticleDOI
TL;DR: In vivo, the steady state content of fibronectin messenger RNA and protein was highest in abnormal wounds, less in most normal scars, and lowest in normal skin, while in vitro, fibroblasts from keloids and hypertrophic scars overexpressed fibronECTin in vivo relative to normal skin and normal scar and retain this characteristic in vitro relative tonormal skin.
Abstract: The overproduction of fibronectin and type I collagen in keloids and hypertrophic scars implicates altered regulation of extracellular matrix components as an important aspect of these wound healing pathologies. However, little is known about the similarities and differences in extracellular matrix gene expression during normal and abnormal wound healing. This study compared the content of fibronectin messenger RNA and rates of fibronectin protein biosynthesis in fibroblasts derived from normal skin, normal scar, keloid, and hypertrophic scar. Fibronectin expression was enhanced in cells from both normal and abnormal wounds relative to cells from quiescent normal skin. Matched pairs of normal and keloid fibroblasts from the same individuals were also compared, and three of the four pairs showed higher fibronectin expression by the keloid cells at the levels of messenger RNA and protein synthesis. This was consistent with previous studies showing elevated steady state content of fibronectin in keloid cells relative to normal cells from the same individual. Fibronectin messenger RNA and protein content in the tissues from which these cells were derived was examined by in situ hybridization and immunohistochemistry. These studies revealed that in vivo, the steady state content of fibronectin messenger RNA and protein was highest in abnormal wounds, less in most normal scars, and lowest in normal skin. Thus, fibroblasts from keloids and hypertrophic scars overexpressed fibronectin in vivo relative to normal skin and normal scar and retain this characteristic in vitro relative to normal skin. Although normal scars contained little fibronectin protein and messenger RNA, cultured fibroblasts derived from these scars had contents of fibronectin messenger RNA and rates of biosynthesis in vitro similar to those of keloid fibroblasts. This indicates that the fibronectin regulatory pathway in scar fibroblasts is influenced by the tissue environment. These results are discussed with respect to the relationship of fibronectin expression in keloids, hypertrophic scars, and normal wounds in human beings.

26 citations


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

  • ...Excessive deposition of fibronectin may contribute, at least in part, to hypertrophic scar formation (30)....

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Journal ArticleDOI
TL;DR: Administration of bFGF for suppression of collagen type I generation could suppress scar tissue formation and reduce connective strength with adjacent teeth and palatal bone.
Abstract: Objective. The purpose of this study was to evaluate the effect of basic fibroblast growth factor (bFGF) on collagen changes after mucoperiosteal denudation of rat palate. Material and methods. A total of 36 male Wistar rats were divided into control, scar, sham, and bFGF groups. In the scar, sham, and bFGF groups, lateral palatal mucoperiosteum was excised to form scar tissue on the palate. In the bFGF group, bFGF solution was injected into the operated area 1 week postoperatively. At 6 weeks postoperatively, the distribution of collagen type I and the 3-dimensional structure of collagen fibers were investigated under immunofluorescent and scanning electron microscopy. Result. In the bFGF group, weakly immunostained submucosa was clearly distinguishable from the strongly immunostained cervical periodontal ligament and gingiva. Collagen fibers running from submucosal tissue into the surface of underlying palatal bone comprised loosely arranged collagen fibrils. Lumen structures in collagen fibers resemble...

15 citations


Additional excerpts

  • ...The reduction of type I collagen production was also observed under immunofluorescent and scanning electron microscopy after administration of bFGF for 6 weeks (24)....

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