Fibronectin (FN) in hypertrophic scars and keloids

Summary Fibronectin (FN) distribution was compared among samples of normal human dermis, hypertrophic scar, keloid, and granulation tissues from deep injuries. Localization was established by use of fibronectin antibodies and the indirect immunofluorescence method. Fresh-frozen tissue was sectioned on a cryostat and examined by epifluorescence. Hypertrophic scar and keloid demonstrated heavy deposition of FN, which conformed to the nodular characteristics of the lesions. Intense localization occurred in granulation tissue over fibroblasts which were stellate and vesiculated, and over small blood vessels. FN-staining was weak in areas over fibroblasts which were more rounded and nonvesiculated. Staining for FN was also minimal over the collagen in normal dermis and the deeper, larger collagen fascicles in the lesions. Fibroblasts cultured from normal dermis, hypertrophic scar, and keloid for 5–6 weeks were intensely stained for FN. Extracellular matrix was heavily positive in cultures from the lesions compared with those from normal dermis.Supported in part by NIH Research Grant 1 R01GM 25159     

Autofluorescence imaging for recurrence detection in skin cancer postoperative scars

This clinical study is a first attempt to use autofluorescence for recurrence diagnosis of skin cancer in postoperative scars. The proposed diagnostic parameter is based on a reduction in scar autofluorescence, evaluated in the green spectral channel. The validity of the method has been tested on 110 postoperative scars from 56 patients suspected of non‐melanoma skin cancer, with eight patients (13 scars) available for the repeated examination. The recurrence diagnosis within a scar has been made after two subsequent autofluorescence check‐ups, representing the temporal difference between the scar autofluorescence amplitudes as a vector. The recognition of recurrence has been discussed to represent the significant deviations from the value of vector angle θ. This new autofluorescence‐based method can be easily integrated into the postoperative monitoring of surgical scars and can help diagnose the recurrence of skin cancer from the early stage of scar development.     

Scarless fetal skin wound healing update

Scar formation, a physiologic process in adult wound healing, can have devastating effects for patients; a multitude of pathologic outcomes, affecting all organ systems, stems from an amplification of this process. In contrast to adult wound repair, the early‐gestation fetal skin wound heals without scar formation, a phenomenon that appears to be intrinsic to fetal skin. An intensive research effort has focused on unraveling the mechanisms that underlie scarless fetal wound healing in an attempt to improve the quality of healing in both children and adults. Unique properties of fetal cells, extracellular matrix, cytokine profile, and gene expression contribute to this scarless repair. Despite the great increase in knowledge gained over the past decades, the precise mechanisms regulating scarless fetal healing remain unknown. Herein, we describe the current proposed mechanisms underlying fetal scarless wound healing in an effort to recapitulate the fetal phenotype in the postnatal environment. Birth Defects Research (Part C) 96:237–247, 2012. © 2012 Wiley Periodicals, Inc.     

In vivo terahertz reflection imaging of human scars during and after the healing process

We use terahertz imaging to measure four human skin scars in vivo. Clear contrast between the refractive index of the scar and surrounding tissue was observed for all of the scars, despite some being difficult to see with the naked eye. Additionally, we monitored the healing process of a hypertrophic scar. We found that the contrast in the absorption coefficient became less prominent after a few months post‐injury, but that the contrast in the refractive index was still significant even months post‐injury. Our results demonstrate the capability of terahertz imaging to quantitatively measure subtle changes in skin properties and this may be useful for improving scar treatment and management.

     

Dating lightning: Dendrochronological and magnetic analyses of lightning scars

Lightning impacts on forests and trees are still understudied from a tree-ring perspective. Lighting causes direct and indirect damages on forests and trees. Trees struck by lightning can show a growth reduction and lightning storms also trigger wildfires in seasonally dry areas such as Mediterranean mountains. Here we combined dendroecological and magnetic analyses to reconstruct and assess the impact of lightning on radial growth and the magnetic properties of wood in Scots pine (Pinus sylvestris) and Black pine (Pinus nigra) in two sites with a high density of lightning impacts located in eastern Spain. We dated several lightning scars, particularly in Scots pine, formed during 1982, when a wildfire was initiated by lightning during a dry summer storm. Growth was reduced during the year when the scar was formed in both pine species, albeit this effect could be masked or amplified by other disturbances (drought, outbreaks). However, despite that short-term growth reduction scarred trees showed higher growth rates than non-scarred trees in the case of Scots pine. The intensity of magnetization did not significantly differ in wood produced before and after the lightning scar was formed. This could be due to multiple lightning hits in the same or nearby stands affecting the magnetization of wood. Wood magnetic properties should be further explored as proxies of lightning impacts in sites where scars are not formed and tree-ring information is limited such as tropical forests. Further cross-disciplinary research is required to assess the impacts of lightning on tree growth and magnetism.     

Attenuation corrected-optical coherence tomography for quantitative assessment of skin wound healing and scar morphology

Imaging the structural modifications of underlying tissues is vital to monitor wound healing. Optical coherence tomography (OCT) images high-resolution sub-surface information, but suffers a loss of intensity with depth, limiting quantification. Hence correcting the attenuation loss is important. We performed swept source-OCT of full-thickness excision wounds for 300 days in mice skin. We used single-scatter attenuation models to determine and correct the attenuation loss in the images. The phantom studies established the correspondence of corrected-OCT intensity (reflectivity) with matrix density and hydration. We histologically validated the corrected-OCT and measured the wound healing rate. We noted two distinct phases of healing—rapid and steady-state. We also detected two compartments in normal scars using corrected OCT that otherwise were not visible in the OCT scans. The OCT reflectivity in the scar compartments corresponded to distinct cell populations, mechanical properties and composition. OCT reflectivity has potential applications in evaluating the therapeutic efficacy of healing and characterizing scars.     

Beyond skin color: emerging roles of melanin-concentrating hormone in energy homeostasis and other physiological functions

Melanin-concentrating hormone (MCH) is a cyclic peptide that mediates its effects by the activation of two G-protein-coupled seven transmembrane receptors (MCHR1 and MCHR2) in humans. In contrast to its primary role in regulating skin color in fish, MCH has evolved in mammals to regulate dynamic physiological functions, from food intake and energy expenditure to behavior and emotion. Chronic infusion or transgenic expression of MCH stimulates feeding and increases adipocity, whereas targeted deletion of MCH or its receptor (MCHR1) leads to resistance to diet-induced obesity with increased energy expenditure and thermogenesis. The involvement of MCH in energy homeostasis and in brain activity has also been validated in mice treated with non-peptide antagonists, suggesting that blockade of MCHR1 could provide a viable approach for treatment of obesity and certain neurological disorders. This review focuses on emerging roles of MCH in regulating central and peripheral mechanisms.     

Initiation of limb regeneration: the critical steps for regenerative capacity

While urodele amphibians (newts and salamanders) can regenerate limbs as adults, other tetrapods (reptiles, birds and mammals) cannot and just undergo wound healing. In adult mammals such as mice and humans, the wound heals and a scar is formed after injury, while wound healing is completed without scarring in an embryonic mouse. Completion of regeneration and wound healing takes a long time in regenerative and non-regenerative limbs, respectively. However, it is the early steps that are critical for determining the extent of regenerative response after limb amputation, ranging from wound healing with scar formation, scar-free wound healing, hypomorphic limb regeneration to complete limb regeneration. In addition to the accumulation of information on gene expression during limb regeneration, functional analysis of signaling molecules has recently shown important roles of fibroblast growth factor (FGF), Wnt/beta-catenin and bone morphogenic protein (BMP)/Msx signaling. Here, the routine steps of wound healing/limb regeneration and signaling molecules specifically involved in limb regeneration are summarized. Regeneration of embryonic mouse digit tips and anuran amphibian (Xenopus) limbs shows intermediate regenerative responses between the two extremes, those of adult mammals (least regenerative) and urodele amphibians (more regenerative), providing a range of models to study the various abilities of limbs to regenerate.     

The molecular mechanism of hypertrophic scar

Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder which often develops after thermal or traumatic injury to the deep regions of the skin and is characterized by excessive deposition and alterations in morphology of collagen and other extracellular matrix (ECM) proteins. HTS are cosmetically disfiguring and can cause functional problems that often recur despite surgical attempts to remove or improve the scars. In this review, the roles of various fibrotic and anti-fibrotic molecules are discussed in order to improve our understanding of the molecular mechanism of the pathogenesis of HTS. These molecules include growth factors, cytokines, ECM molecules, and proteolytic enzymes. By exploring the mechanisms of this form of dermal fibrosis, we seek to provide some insight into this form of dermal fibrosis that may allow clinicians to improve treatment and prevention in the future.     

Modulatory effects of connexin-43 expression on gap junction intercellular communications with mast cells and fibroblasts

The influence of mast cells upon aberrant wound repair and excessive fibrosis has supportive evidence, but the mechanism for these mast cell activities is unclear. It is proposed that heterocellular gap junction intercellular communication (GJIC) between fibroblasts and mast cells directs some fibroblast activities. An in vitro model was used employing a rodent derived peritoneal mast cell line (RMC-1) and human dermal derived fibroblasts. The influence of the expression of the gap junction channel structural protein, connexin 43 (Cx-43) on heterocellular GJIC, the expression of microtubule β-tubulin and microfilament α smooth muscle actin (SMA) were investigated. The knockdown of Cx-43 by siRNA in RMC-1 cells completely blocked GJIC between RMC-1 cells. SiRNA knockdown of Cx-43 within fibroblasts only dampened GJIC between fibroblasts. It appears Cx-43 is the only expressed connexin (Cx) in RMC-1 cells. Fibroblasts express other Cxs that participate in GJIC between fibroblasts in the absence of Cx-43 expression. Heterocellular GJIC between RMC-1 cells and fibroblasts transformed fibroblasts into myofibroblasts, expressing α SMA within cytoplasmic stress fibers. The knockdown of Cx-43 in RMC-1 cells increased β-tubulin expression, but its knockdown in fibroblasts reduced β-tubulin expression. Knocking down the expression of Cx-43 in fibroblasts limited αSMA expression. Cx-43 participation is critical for heterocellular GJIC between mast cells and fibroblasts, which may herald a novel direction for controlling fibrosis.     

微小RNA miR-21在皮肤创伤愈合中的研究进展

微小RNA是一类真核细胞中广泛存在的内源性转录后调控分子,其在细胞的增殖、分化、凋亡、迁移等过程中发挥了重要的调控作用。皮肤创伤修复涉及复杂的细胞与分子的相互作用网络。近年来研究表明micro RNAs在皮肤创伤修复中发挥调控作用,引人关注。miR-21作为重要的癌基因是目前研究的最多的miRNAs分子之一,其在皮肤创伤修复中的作用研究也越来越受到重视。研究表明miR-21参与了细胞增殖与迁移、炎症反应、血管生成和细胞外基质合成等重要修复相关事件的调控。因此,阐明miR-21分子在正常皮肤创伤愈合中的作用,厘清miR-21表达失调在修复不足和修复过度中的功能,将深化我们对于皮肤创伤愈合基本理论的认识,并为促进创面愈合与防治修复不足和过度提供潜在的治疗靶点。本文就miR-21分子在正常皮肤创伤修复、慢性难愈性创面和增生性瘢痕中作用的研究进展进行综述展望。     

Molecular Changes Underlying Genistein Treatment of Wound Healing: A Review

Estrogen deprivation is one of the major factors responsible for many age-related processes including poor wound healing in postmenopausal women. However, the reported side-effects of estrogen replacement therapy (ERT) have precluded broad clinical administration. Therefore, selective estrogen receptor modulators (SERMs) have been developed to overcome the detrimental side effects of ERT on breast and/or uterine tissues. The use of natural products isolated from plants (e.g., soy) may represent a promising source of biologically active compounds (e.g., genistein) as efficient alternatives to conventional treatment. Genistein as natural SERM has the unique ability to selectively act as agonist or antagonist in a tissue-specific manner, i.e., it improves skin repair and simultaneously exerts anti-cancer and chemopreventive properties. Hence, we present here a wound healing phases-based review of the most studied naturally occurring SERM.