Differential Expression of Fibromodulin, a Transforming Growth Factor-β Modulator, in Fetal Skin Development and Scarless Repair

Soo, Chia; Hu, Fei-Ya; Zhang, Xinli; Wang, Yubert; Beanes, Steven R.; Lorenz, H. Peter; Hedrick, Marc H.; Mackool, Richard J.; Plaas, Ana; Kim, Soojin; Longaker, Michael T.; Freymiller, Earl; Ting, Kang

doi:10.1016/s0002-9440(10)64555-5

Cited by 169 publications

(166 citation statements)

References 34 publications

(42 reference statements)

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“…In our microarray data, significant increases were seen in matrix proteins such as fibromodulin (FMOD) and collagens compared to old cells and these data correspond to the literature (Mast et al, 1993;Hallock et al, 1993;Soo et al, 2000Soo et al, , 2002. FMOD was also significantly higher in the RT-PCR which was one of the random probes selected for confirmation of the microarray data.…”

Section: Discussionsupporting

confidence: 89%

“…The most significantly expressed gene in the microarray data, EFEMP-1 or Fibulin 3 (FPLN-3) is homologous to FBLN-5 and are widely expressed ECM proteins known to regulate cell proliferation and have also been shown to antagonize angiogenesis. FBLN-5 has been shown to promote wound healing in vivo using a retroviral gene transfer to dermal wounds of rabbits showing 50% net increase of newly formed granulation tissue and wound closure (Lee et al, 2004;Albig et al, 2006;Soo et al, 2000). Microarray analysis has also shown the importance of ECM glypicans which are proteins that can bind a multitude of GF and ECM molecules which are implicated in signal transduction cascaded that most likely regulate cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

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Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells

Ramelet¹,

Hirt‐Burri

Raffoul³

et al. 2009

Experimental Gerontology

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a b s t r a c tEngineering of fetal tissue has a high potential for the treatment of acute and chronic wounds of the skin in humans as these cells have high expansion capacity under simple culture conditions and one organ donation can produce Master Cell Banks which can fabricate over 900 million biological bandages (9 Â 12 cm). In a Phase 1 clinical safety study, cases are presented for the treatment of therapy resistant leg ulcers. All eight patients, representing 13 ulcers, tolerated multiple treatments with fetal biological bandages showing no negative secondary effects and repair processes similar to that seen in 3rd degree burns. Differential gene profiling using Affymetrix gene chips (analyzing 12,500 genes) were accomplished on these banked fetal dermal skin cells compared to banked dermal skin cells of an aged donor in order to point to potential indicators of wound healing. Families of genes involved in cell adhesion and extracellular matrix, cell cycle, cellular signaling, development and immune response show significant differences in regulation between banked fetal and those from banked old skin cells: with approximately 47.0% of genes over-expressed in fetal fibroblasts. It is perhaps these differences which contribute to efficient tissue repair seen in the clinic with fetal cell therapy.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells

Ramelet¹,

Hirt‐Burri

Raffoul³

et al. 2009

Experimental Gerontology

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“…In contrast to VeGF, pDGF has a prolonged expression during scar formation, but disappears quickly in fetal wounds (61).…”

Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 90%

Radiotherapy and wound healing: Principles, management and prospects (Review)

Gieringer

Gosepath²,

Naim³

2011

Oncol Rep

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Abstract. radiation therapy is a major therapeutic modality in the management of cancer patients. Over 60% of these patients receive radiotherapy at some point during their course of treatment and over 90% will develop skin reactions after therapy. problematic wound healing in radiation-damaged tissue constitutes a major surgical difficulty and despite all efforts, irradiated skin remains a therapeutic challenge. this review provides an overview of the fundamental principles of radiation therapy with regards to the wound healing in normal and irradiated skin. Furthermore, it presents techniques that describe how to prevent and manage skin side effects as well as prospects that may improve cutaneous wound repair in general and in irradiated skin.

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“…3,9 We previously reported a significant decrease of fibromodulin (Fm) expression associated with the transition from scarless fetal-type to adult-type repair with scar. 13 Fibromodulin protein (FM) is a small leucine-rich proteoglycan involved in angiogenesis and fibrillogenesis, 14e18 but its role in fetal and adult cutaneous repair is not fully understood. Our current study used Fm loss-and gain-of-function wound models to determine the necessity and sufficiency of FM in fetal scarless healing.…”

mentioning

confidence: 99%

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing

Zheng

Zhang

Dang

et al. 2016

The American Journal of Pathology

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In contrast to adult and late-gestation fetal skin wounds, which heal with scar, early-gestation fetal skin wounds display a remarkable capacity to heal scarlessly. Although the underlying mechanism of this transition from fetal-type scarless healing to adult-type healing with scar has been actively investigated for decades, in utero restoration of scarless healing in late-gestation fetal wounds has not been reported. In this study, using loss-and gain-of-function rodent fetal wound models, we identified that fibromodulin (Fm) is essential for fetal-type scarless wound healing. In particular, we found that loss of Fm can eliminate the ability of early-gestation fetal rodents to heal without scar. Meanwhile, administration of fibromodulin protein (FM) alone was capable of restoring scarless healing in lategestation rat fetal wounds, which naturally heal with scar, as characterized by dermal appendage restoration and organized collagen architectures that were virtually indistinguishable from those in age-matched unwounded skin. High Fm levels correlated with decreased transforming growth factor (TGF)-b1 expression and scarless repair, while low Fm levels correlated with increased TGF-b1 expression and scar formation. This study represents the first successful in utero attempt to induce scarless repair in late-gestation fetal wounds by using a single protein, Fm, and highlights the crucial role that the FMeTGF-b1 nexus plays in fetal-type scarless skin repair. (Am J Pathol 2016 http://dx

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Differential Expression of Fibromodulin, a Transforming Growth Factor-β Modulator, in Fetal Skin Development and Scarless Repair

Cited by 169 publications

References 34 publications

Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells

Chronic wound healing by fetal cell therapy may be explained by differential gene profiling observed in fetal versus old skin cells

Radiotherapy and wound healing: Principles, management and prospects (Review)

Fibromodulin Is Essential for Fetal-Type Scarless Cutaneous Wound Healing

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