Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

Eto, Hikaru; Suga, Hirotaka; Aoi, Noriyuki; Kato, Harunosuke; Doi, Kentaro; Kuno, Shinichiro; Tabata, Yasuhiko; Yoshimura, Kotaro

doi:10.1038/labinvest.2011.127

Cited by 78 publications

(60 citation statements)

References 44 publications

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“…130,131 There is relatively strong expression of TIMP-1 in hypertrophic scar biopsies in contrast to very low levels of TIMP-1 in normal skin. 92 Less synthesis of molecules that promote matrix breakdown (e.g., MMPs) may also explain the lack of scar regression seen in keloids.…”

Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Xue

Jackson

2015

Advances in Wound Care

985

828

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Significance: When a cutaneous injury occurs, the wound heals via a dynamic series of physiological events, including coagulation, granulation tissue formation, re-epithelialization, and extracellular matrix (ECM) remodeling. The final stage can take many months, yet the new ECM forms a scar that never achieves the flexibility or strength of the original tissue. In certain circumstances, the normal scar is replaced by pathological fibrotic tissue, which results in hypertrophic or keloid scars. These scars cause significant morbidity through physical dysfunction and psychological stress. Recent Advances and Critical Issues: The cutaneous ECM comprises a complex assortment of proteins that was traditionally thought to simply provide structural integrity and scaffolding characteristics. However, recent findings show that the ECM has multiple functions, including, storage and delivery of growth factors and cytokines, tissue repair and various physiological functions. Abnormal ECM reconstruction during wound healing contributes to the formation of hypertrophic and keloid scars. Whereas adult wounds heal with scarring, the developing foetus has the ability to heal wounds in a scarless fashion by regenerating skin and restoring the normal ECM architecture, strength, and function. Recent studies show that the lack of inflammation in fetal wounds contributes to this perfect healing. Future Directions: Better understanding of the exact roles of ECM components in scarring will allow us to produce therapeutic agents to prevent hypertrophic and keloid scars. This review will focus on the components of the ECM and their role in both physiological and pathological (hypertrophic and keloid) cutaneous scar formation. SCOPE AND SIGNIFICANCEThis article reviews the extracellular matrix (ECM) and its remodeling during normal cutaneous wound healing and scar formation, and the differential response of the components of the ECM and their role in pathological (hypertrophic and keloid) cutaneous scar formation. This review focuses on the major players involved in the irregular ECM production as being; fibroblasts and their immature counterparts, myofibroblasts; collagens; transforming growth factor (TGF)-b, which controls the production of collagens; proteoglycans and matrix metalloproteinases (MMPs). We also highlight the complexity of interactions occurring in the ECM of skin during (ab) normal scar formation. TRANSLATIONAL RELEVANCEAbnormal ECM, particularly abnormal collagen remodeling and reorganization, accounts for one of the most important contributing factors to abnormal scarring. Identification of the exact ECM molecules involved in causing abnormal scarring is likely to provide a future treatment target. This may be achieved by promoting the correct balance in collagen ratios or by directly targeting the production of collagen. Overall, a better understanding of the exact roles of ECM components in scarring will help us to produce therapeutic agents to prevent and treat hypertrophic and keloid scars. CLINICAL RELEVANCEThere ...

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Section: Matrix Metalloproteinasesmentioning

confidence: 99%

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Xue

Jackson

2015

Advances in Wound Care

985

828

View full text Add to dashboard Cite

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“…However, Eto et al (2012) demonstrated that FGF2 promoted cell proliferation in normal skin-derived fibroblasts, downregulating the expression of collagen (type 1 and 3) and a-SMA, whilst increasing HGF gene expression.…”

Section: Discussionmentioning

confidence: 98%

The role of FGF-2/HGF and fibronectin matrix on pleomorphic adenoma myoepithelial cell morphology and immunophenotype: anin vitrostudy

Silva¹,

Nardello

Garcia

et al. 2014

Growth Factors

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Myoepithelial cells play a central role in glandular tumors, regulating the progression of in situ to invasive neoplasias, with the tumor microenvironment being shown to be involved in both initiation and progression. This study aimed to analyze the in vitro effects of fibroblast growth factor-2 (FGF-2) and hepatocyte growth factor (HGF) in myoepithelial cells under the influence of the fibronectin matrix extracellular protein. Benign myoepithelial cells were obtained from pleomorphic adenoma and cultured on a fibronectin substratum. FGF-2 and HGF were supplemented at different concentrations and time intervals, in order to evaluate cell proliferation, morphology and immunophenotype. Individually, FGF-2 and HGF supplementation did not alter myoepithelial cell proliferation, morphology or immunophenotype. The fibronectin substratum provoked an increase in cell proliferation and immunopositivity for α-smooth muscle actin and FGF-2. The myoepithelial cell morphology changed when the fibronectin substratum and FGF-2 acted together, highlighting the importance of the fibronectin extracellular matrix protein on the behavior of these cells.

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“…We also reviewed previous related studies and found most of those were about changes on MMPs less than 5 days after intervention [44][45][46], lacking long-term observation reports. On the other hand, in the cell-based experiments, changes in the concentration of MMPs could be accurately detected by ELISA, and we conducted an ELISA experiment within 48 h; therefore, we were able to observe changes between the treated and untreated groups.…”

Section: Discussionmentioning

confidence: 99%

Antiphotoaging Effect of Conditioned Medium of Dedifferentiated Adipocytes on Skin In Vivo and In Vitro: A Mechanistic Study

Zhang

Xu³

et al. 2015

Stem Cells and Development

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Photoaging of skin occurs partially due to decreased synthesis and increased degradation of dermal collagen. Antiphotoaging therapy aims to counteract these effects. This study aimed to investigate whether secretory factors from dedifferentiated adipocytes (DAs) could alleviate photoaging in human dermal fibroblasts (HDFs) and in mice and to clarify the underlying mechanism. DAs were acquired and verified based on cellular biomarkers and multilineage differentiation potential. The concentrations of several cytokines in conditioned medium from DAs (DA-CM) were determined. In vivo pathological changes, collagen types I and III, and matrix metalloproteinase (MMP)-1 and -3 were evaluated following the injection of 10-fold concentrated DA-CM into photoaged mice. In vitro, the effect of DA-CM on stress-induced premature senescence in HDFs was investigated by 5-ethynyl-2¢-deoxyuridine (EdU) staining and b-galactosidase staining. The influence of DA-CM and transforming growth factor-b 1 (TGF-b 1 ) on the secretion of collagen types I and III, MMP-1, and MMP-3 in HDFs was evaluated by ELISA. In vivo, we found that subcutaneously injected 10-fold concentrated DA-CM increased the expression of collagen types I and III. In vitro, DA-CM clearly mitigated the decreased cell proliferation and delayed the senescence status in HDFs induced by ultraviolet B (UVB). HDFs treated with DA-CM exhibited higher collagen types I and III secretion and significantly lower MMP-1 and MMP-3 secretion. The TGF-b 1 -neutralizing antibody could partially reduce the recovery effect. Our results suggest that DAs may be useful for aging skin and their effects are mainly due to secreted factors, especially TGF-b 1 , which stimulate collagen synthesis and alleviate collagen degradation in HDFs.

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Therapeutic potential of fibroblast growth factor-2 for hypertrophic scars: upregulation of MMP-1 and HGF expression

Cited by 78 publications

References 44 publications

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

Extracellular Matrix Reorganization During Wound Healing and Its Impact on Abnormal Scarring

The role of FGF-2/HGF and fibronectin matrix on pleomorphic adenoma myoepithelial cell morphology and immunophenotype: anin vitrostudy

Antiphotoaging Effect of Conditioned Medium of Dedifferentiated Adipocytes on Skin In Vivo and In Vitro: A Mechanistic Study

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