Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging.

During aging, stromal functions are thought to be impaired, but little is known whether this stems from changes of fibroblasts. Using population- and single-cell transcriptomics, as well as long-term lineage tracing, we studied whether murine dermal fibroblasts are altered during physiological aging under different dietary regimes that affect longevity. We show that the identity of old fibroblasts becomes undefined, with the fibroblast states present in young skin no longer clearly demarcated. In addition, old fibroblasts not only reduce the expression of genes involved in the formation of the extracellular matrix, but also gain adipogenic traits, paradoxically becoming more similar to neonatal pro-adipogenic fibroblasts. These alterations are sensitive to systemic metabolic changes: long-term caloric restriction reversibly prevents them, whereas a high-fat diet potentiates them. Our results therefore highlight loss of cell identity and the acquisition of adipogenic traits as a mechanism underlying cellular aging, which is influenced by systemic metabolism.

STAT1 modulates tissue wasting or overgrowth downstream from PDGFRß.

Platelet-derived growth factor (PDGF) acts through two conserved receptor tyrosine kinases: PDGFRα and PDGFRß. Gain-of-function mutations in human PDGFRB have been linked recently to genetic diseases characterized by connective tissue wasting (Penttinen syndrome) or overgrowth (Kosaki overgrowth syndrome), but it is unclear whether PDGFRB mutations alone are responsible. Mice with constitutive PDGFRß signaling caused by a kinase domain mutation (D849V) develop lethal autoinflammation. Here we used a genetic approach to investigate the mechanism of autoinflammation in Pdgfrb+/D849V mice and test the hypothesis that signal transducer and activator of transcription 1 (STAT1) mediates this phenotype. We show that Pdgfrb+/D849V mice with Stat1 knockout (Stat1-/-Pdgfrb+/D849V ) are rescued from autoinflammation and have improved life span compared with Stat1+/-Pdgfrb+/D849V mice. Furthermore, PDGFRß-STAT1 signaling suppresses PDGFRß itself. Thus, Stat1-/-Pdgfrb+/D849V fibroblasts exhibit increased PDGFRß signaling, and mice develop progressive overgrowth, a distinct phenotype from the wasting seen in Stat1+/-Pdgfrb+/D849V mice. Deletion of interferon receptors (Ifnar1 or Ifngr1) does not rescue wasting in Pdgfrb+/D849V mice, indicating that interferons are not required for autoinflammation. These results provide functional evidence that elevated PDGFRß signaling causes tissue wasting or overgrowth reminiscent of human genetic syndromes and that the STAT1 pathway is a crucial modulator of this phenotypic spectrum.

Cyclic growth of dermal papilla and regeneration of follicular mesenchymal components during feather cycling.

How dermis maintains tissue homeostasis in cyclic growth and wounding is a fundamental unsolved question. Here, we study how dermal components of feather follicles undergo physiological (molting) and plucking injury-induced regeneration in chickens. Proliferation analyses reveal quiescent, transient-amplifying (TA) and long-term label-retaining dermal cell (LRDC) states. During the growth phase, LRDCs are activated to make new dermal components with distinct cellular flows. Dermal TA cells, enriched in the proximal follicle, generate both peripheral pulp, which extends distally to expand the epithelial-mesenchymal interactive interface for barb patterning, and central pulp, which provides nutrition. Entering the resting phase, LRDCs, accompanying collar bulge epidermal label-retaining cells, descend to the apical dermal papilla. In the next cycle, these apical dermal papilla LRDCs are re-activated to become new pulp progenitor TA cells. In the growth phase, lower dermal sheath can generate dermal papilla and pulp. Transcriptome analyses identify marker genes and highlight molecular signaling associated with dermal specification. We compare the cyclic topological changes with those of the hair follicle, a convergently evolved follicle configuration. This work presents a model for analyzing homeostasis and tissue remodeling of mesenchymal progenitors.

Implications for cumulative and prolonged clinical improvement induced by cross-linked hyaluronic acid: An in vivo biochemical/microscopic study in humans.

In photoaged human skin, type I collagen fragmentation impairs dermal extracellular matrix (ECM) integrity, resulting in collapsed/contracted fibroblasts with reduced type I procollagen synthesis. Injections of cross-linked hyaluronic acid (CL-HA) reverse these deleterious changes. To investigate the time course and effects of biochemical changes induced by injected CL-HA, particularly whether fibroblast activation leads to accumulation/deposition of dermal collagen, we injected CL-HA into photoaged skin of human participants over 60 years-old and performed biochemical/microscopic analyses of skin samples. Beginning 1 week post-injection and lasting 6-9 months, fibroblasts exhibited activation, including increased immunostaining and gene expression of markers of type I collagen synthesis, such as heat shock protein 47 and components of the transforming growth factor-ß pathway. At 1 week post-injection, multiphoton microscopy revealed elongation/stretching of fibroblasts, indicating enhanced dermal mechanical support. At 4 weeks, second-harmonic generation microscopy revealed thick collagen bundles densely packed around pools of injected CL-HA. At 12 months, accumulation of thick collagen bundles was observed and injected CL-HA remained present in substantial amounts. Thus, by occupying space in the dermal ECM, injected CL-HA rapidly and durably enhances mechanical support, stimulating fibroblast elongation and activation, which results in thick, densely packed type I collagen bundles accumulating as early as 4 weeks post-injection and continuing for at least a year. These observations indicate that early and prolonged clinical improvement following CL-HA injection results from space-filling and collagen deposition. As type I collagen has an estimated half-life of 15 years, our data provide the foundations for optimizing the timing/frequency of repeat CL-HA injections.

Nevus lipomatosus superficialis: A series of six cases.

Nevus lipomatosus still imposes diagnostic, categorization, and etiologic challenges. Even though an intradermal adipose tissue is a histopathologic prerequisite, the lesions are clinically divided into classic multiple forms and a solitary variant, which some consider a separate so-called lipofibroma clinicopathologic entity. This further complicates the true prevalence, classification and etiopathogenesis of nevus lipomatosus. Case reports and series studies have reflected either consistent or variable and sometimes conflicting clinicopathologic findings. A few have reported electron microscopic findings. Immunohistochemistry is lacking. We report two multiple and four solitary forms of nevus lipomatosus in six patients, highlighting their salient histopathologic features and immunohistochemical profile. Both forms showed intradermal groups of perivascular S100+ lipogenic and CD34+ mesenchymal cells intermixed with scattered CD1a+ and FXIIIa+ dendrocytes, CD3 lymphocytic and CD117 mast cells in a fibromyxoid milieu. Epidermal nevoid and comedonal follicular alterations, attenuated dermal connective tissue and adnexal structures were variably present in both forms. We compared our findings with seven series of studies reporting classic and solitary forms. Both forms showed similar histopathologic findings, comparable clinicopathologic features, predominantly pelvic, and shoulder girdle distribution patterns in bimodal age onsets. Even though some lipomatous skin lesions clinically and histopathologically overlap with nevus lipomatosus, certain findings are helpful distinguishing features. Small intradermal islands of lipocytic fibroplasia have characteristic perivascular milieu that may function as a niche of preadipose CD34 mesenchymal stem cells. They are most likely represented in the dermis of the pelvic and shoulder areas in certain individuals prone to maintain these embryonic reservoirs, which are clinically manifested at different ages. Some may have unifocal or multifocal residues reflecting multiple and solitary forms.

Superficial desmoplastic fibroblastoma (collagenous fibroma): Clinicopathologic study of 11 cases.

BACKGROUND: Desmoplastic fibroblastoma (collagenous fibroma) is a rare soft tissue tumor that usually arises in the subcutis or skeletal muscle. Cases superficial to fascia are unusual and can cause diagnostic difficulty. We present 11 cases of superficial desmoplastic fibroblastoma involving a wide anatomic distribution. METHODS: Archives were searched using the term "desmoplastic fibroblastoma" over a 10-year period (2012-2022). Cases superficial to fascia were retrieved, and available clinicopathologic features were recorded. Only cases involving the dermis were included. RESULTS: Eleven cases were identified, all of which were received in consultation. Tumors involved the head and neck (2), lower extremity (2), back (2), foot (1), shoulder (1), axilla (1), hand (1), and breast (1). Each consisted of a hypocellular proliferation of bland stellate to spindled fibroblasts set in a collagenous to focally myxoid stroma. The immunohistochemical stains available for review demonstrated SMA positivity (4/7) and negative immunoreactivity for CD34 (0/6), EMA (0/3), desmin (0/3), and S100 (0/7). CONCLUSIONS: Desmoplastic fibroblastoma may present superficially in the dermis to subcutis, posing a potential source of diagnostic difficulty. Recognition of the characteristic histopathologic features of desmoplastic fibroblastoma with judicial use of immunohistochemical stains should allow for accurate diagnosis.

Immunofluorescence findings in a reactivating lichenoid photoallergic chronic dermatitis (actinic reticuloid).

BACKGROUND: Chronic photosensitivity dermatitis (CPD) (also named actinic reticuloid) is an unusual disease classically referred often in elderly men. Affected patients have severely itchy, thickened dry skin in areas exposed to the sun throughout the years. METHOD: A Caucasian female patient who worked most of her life outside who had "chronic dermatitis" in her neck started planting chrysanthemum in her garden on a sunny day. Later, she presented edema, erythema, papules, and a few vesicles in her neck with severe pruritus. STUDIES: A skin biopsy revealed the diagnosis of CPD, along with positive testing for ultraviolet B (UVB), minimal erythema doses (MED) for UVB (MEDB) UVA (MEDA) and PhotoPath. RESULTS: Direct immunofluorescence (DIF) stains using anti-human antibodies against fibrinogen, albumin, IgG, IgM, lambda, kappa, and C3c and C1q were positive at the base membrane area of the dermal epidermal junction, in the papillary dermis, as well as the neurovascular bundles in all the dermis and the extracellular matrix, especially those under the blisters. CONCLUSION: With this case, we suggest not forgetting the importance of using DIF in reactivated CPD cases in addition to the photo patch testing.

Correlation between the efficacy of picosecond-domain laser treatment for solar lentigo and the vascularity in the upper dermis using optical coherence tomography angiography in Asian women.

OBJECTIVES: The purpose of this study was to noninvasively confirm the characteristics of the dermal vasculature in patients with solar lentigo (SL) and determine any association with the efficacy of picosecond-domain laser (PSL) treatment. METHODS: Thirteen facial SL lesions in 11 Asian female patients were included in this study and evaluated over 12 weeks. An Nd:YAG laser was used at 532 nm and 750 ps. Skin color and morphological structure were evaluated by ANTERA-3D® and optical coherence tomography (OCT), respectively. To analyze the vascularity in the upper dermis, an OCT angiography (OCTA) algorithm was applied to the OCT data. RESULTS: After PSL treatment, significant improvement in both hyperpigmentation and abnormally thickened epidermis was observed, but the efficacy varied for each lesion. There was a significant correlation between the change in the melanin index due to PSL treatment and preoperative vascular density in the upper dermis. CONCLUSIONS: To the best of our knowledge, this is the first report to demonstrate a correlation between the efficacy of PSL treatment of SL lesions and the vascularity in the upper dermis. Methods to evaluate the vasculature in the upper dermis may be useful for preoperative prediction of the efficacy of PSL treatment for SL lesions.

Mechanical Models of Collagen Networks for Understanding Changes in the Failure Properties of Aging Skin.

Skin undergoes mechanical alterations due to changes in the composition and structure of the collagenous dermis with aging. Previous studies have conflicting findings, with both increased and decreased stiffness reported for aging skin. The underlying structure-function relationships that drive age-related changes are complex and difficult to study individually. One potential contributor to these variations is the accumulation of nonenzymatic crosslinks within collagen fibers, which affect dermal collagen remodeling and mechanical properties. Specifically, these crosslinks make individual fibers stiffer in their plastic loading region and lead to increased fragmentation of the collagenous network. To better understand the influence of these changes, we investigated the impact of nonenzymatic crosslink changes on the dermal microstructure using discrete fiber networks representative of the dermal microstructure. Our findings suggest that stiffening the plastic region of collagen's mechanical response has minimal effects on network-level stiffness and failure stresses. Conversely, simulating fragmentation through a loss of connectivity substantially reduces network stiffness and failure stress, while increasing stretch ratios at failure.

3D-Bioprinted Skin Tissues for Improving Wound Healing: Current Status and Perspective.

Advancements in tissue engineering enable the fabrication of complex and functional tissues or organs. In particular, bioprinting enables controlled and accurate deposition of cells, biomaterials, and growth factors to create complex 3D skin constructs specific to a particular individual. Despite these advancements, challenges such as vascularization, long-term stability, and regulatory considerations hinder the clinical translation of bioprinted skin constructs. This chapter focuses on such approaches using advanced biomaterials and bioprinting techniques to overcome the current barriers in wound-healing studies. Moreover, it addresses current obstacles in wound-healing studies, highlighting the need for continued research and innovation to overcome these barriers and facilitate the practical utilization of bioprinted skin constructs in clinical settings.

Application of Artificial Dermis Combined With a Medial Flap From the Second Toe to Repair Degloving Injury of the Fingertip.

There is no standard technique for repairing degloving injuries of the fingertip. Nail bed flap transplantation is a common surgical technique to address this injury, but this procedure inevitably damages the donor site in the toe. This article describes a surgical technique that can restore the appearance of the injured fingernail and preserve the length and function of the injured finger without damaging the toenail.

Artificial dermis combined with negative pressure wound therapy and platelet-rich plasma to treat traumatic wounds: a retrospective study.

OBJECTIVE: The reconstruction of complex soft tissue defects with exposure of bones and tendons represents an increasing challenge in wound care, especially in large extremity wounds. The aim of this study was to detect the clinical efficacy of combined use of negative pressure wound therapy (NPWT), artificial dermis (ADM), platelet-rich plasma (PRP) and split-thickness skin grafting (STSG) in the reconstruction of large traumatic extremity skin defects. METHOD: In this study, eight cases were treated with combined therapies for repairing complex extremity wounds and the results were reviewed retrospectively. After surgical debridement, all wounds received ADM, PRP and delayed STSG, which were all aided with NPWT. RESULTS: The patients consisted of five males and three females, with a mean age of 44 years. A total of six lower extremity wounds were located at the foot/ankle, with exposed tendon in five, bone exposure in three and both in two. Of the group, two patients had exposed tendon on arm/hand wounds. The size of wounds and ADM averaged 126cm2 and 42.3cm2, respectively. ADM was used to cover the exposed bone or tendon, the granulation and muscular tissue were covered with vacuum sealing drainage (VSD) directly, for NPWT. The survival rate of ADM averaged 98.9%. The average time for survival of ADM was 12.8 days and the mean uptake of autologous skin graft was 93.5%. Only one patient received repeated skin grafts. All patients achieved successful healing and reported no complications. The mean length of hospital stay was 36.1 days. CONCLUSION: Our study revealed that ADM in conjunction with NPWT, PRP and STSG could be used for repairing large traumatic extremity wounds. Wound closure was achieved without flaps, the aesthetic and functional outcomes were acceptable, and only one patient developed a 35% loss of skin graft. DECLARATION OF INTEREST: This work was supported by grants from the Natural Science Foundation of Hubei Province (grant no. 2020CFB464) and Youth Foundation of Wuhan Municipal Health Commission (grant no. WX20Q15). The authors have no conflicts of interest to declare.

Three-dimensional adipofascial and dermal structures involved in forehead crease formation.

Deeply etched forehead creases indicate aging. Various treatments such as filler injections, fat grafting, and facelift surgery are used to remove them. However, knowledge of the anatomical structures associated with subcutaneous tissue changes and the superficial musculoaponeurotic system is lacking, and there is no consensus about the appropriate treatment. We have investigated the subcutaneous structures involved in forehead creases; this will help to establish selection criteria for improved treatment. The forehead sections of five unfixed adult Asian cadavers were obtained. Tissues containing forehead creases were removed from the periosteum and were examined using gross observation, radiography, histology, and nano-computed tomography. All methods revealed that the dermis in the skin crease area, namely the fold visible from the body surface, was bound to the frontalis muscle by a three-dimensional fibrous structure between the fatty septa. This structure was dense near the skin folds and sparse and thin in other areas. In particular, it was tightly bound to the dermis immediately below the crease, with collagen fibers traversing toward the epidermis. In addition, there were fewer skin appendages near the crease than in the normal area, or they were absent altogether; the epidermis was thicker, and the dermal papillae were more developed. It is thought that the density and firmness of the fibrous fatty septal structures between the dermis-frontalis muscle and the specific structures of the epidermis and dermis immediately below the crease account for the characteristic plastic forehead creases.

Xenogeneic collagen matrix vs. connective tissue graft for the treatment of multiple gingival recession: a systematic review and meta-analysis.

The aim of this systematic review (SR) compared the effect of xenogeneic collagen matrix (XCM) vs. connective tissue graft (CTG) for the treatment of multiple gingival recession (MGR) Miller Class I and II or Cairo type I. Five databases were searched up to August 2022 for randomized clinical trials (RCTs) comparing the clinical effects of XCM vs. CTG in the treatment of MGR. The random effects model of mean differences was used to determine reduction of gingival recession (GR), gain in keratinized tissue width (KTW), gain in gingival thickness (GT) and gain in clinical attachment level (CAL). The risk ratio was used to complete root coverage (CRC) at 6 and 12 months. 10 RCTs, representing 1095 and 649 GR at 6 and 12 months, respectively, were included in this SR. The meta-analysis showed no statistically significant difference in GR reduction, KTW gain GT gain or CAL gain between groups at 6 months. However, at 12 months of follow-up, differences favoring the control group were observed (p < 0.05). CRC was significantly higher in the CTG group at 6 and 12 months. Regarding dentine hypersensitivity (DH), no statistically significant differences were found between groups at 6 and 12 months of follow-up (p < 0.05). At 12 months, CTG showed significantly superior clinical results in the treatment of MGR: however, this difference was not observed in the decrease of DH.

Expanded Polytetrafluoroethylene Combined with Human Acellular Dermis Matrix for the Nasal Reconstruction in Patients with Postoperative Deformities.

INTRODUCTION: Augmentation rhinoplasty is one of five aesthetic surgeries in the world. Expanded polytetrafluoroethylene (ePTFE) has been reported as a rational choice to augment the nasal dorsum and tip. However, its application for nasal tip augmentation has some debates. This study presented a technique using ePTFE grafts combined with human acellular dermis matrix (HADM) to reconstruct a deformed nose caused by previous rhinoplasties. METHODS: 50 female patients who came to the hospital from 08/2022 to 09/2022 for surgical revision of their nasal deformity. ePTFE was applied to reconstruct the nasal dorsum, tip, and columella strut. HADM grafts were utilized to reinforce the reconstructed framework. Patients were evaluated for at least 12 months for both aesthetic and functional results. RESULTS: Postoperatively, the nasal dorsal length increased from 38.9 ± 1.32 to 43.4 ± 1.22 mm; while, the projection of the nasal tip also raised from 19.8 ± 1.16 to 23.9 ± 1.05 mm. 38 patients (76%) reported that their breathing and smelling were improved compared to preoperatively. No cases had implant reactions, extrusion, or warping columella strut. Most of the patients (84%) were satisfied with the surgical outcomes. Three patients (6%) had redness at the nasal tip. The nasal tip of ten patients (20%) was hardened for 3 months postoperatively. There were 6% of patients who developed an infection and 2% of patients had asymmetric soft tissues of the tip 3 postoperative months. CONCLUSION: This technique brought satisfactory aesthetic and functional results to patients, with no extrusion or rejection observed 12 months postoperatively. Infection was a prominent complication that should be considered and strictly monitored. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Development and validation of cryopreserved or freeze-dried decellularized human dermis for transplantation.

For decades, dermal tissue grafts have been used in various regenerative, reconstructive, and augmentative procedures across the body. To eliminate antigenicity and immunogenic response while still preserving the individual components and collective structural integrity of the extracellular matrix (ECM), dermis can be decellularized. Acellular dermal matrix (ADM) products like such are produced to accurately serve diverse clinical purposes. The aim of the present study is to evaluate the efficacy of a novel decellularization protocol of the human dermis, which eliminates residual human genetic material without compromising the biomechanical integrity and collagenous content of the tissue. Moreover, a freeze-drying protocol was validated. The results showed that though our decellularization protocol, human dermis can be decellularized obtaining a biocompatible matrix. The procedure is completely realized in GMP aseptic condition, avoiding tissue terminal sterilization.

Investigation of Two New Grafting Techniques for Dorsal Augmentation Rhinoplasty: An Experimental Study with New Zealand White Rabbits.

INTRODUCTION: Cartilage is an important source in supporting the structure of the nose for dorsal augmentation rhinoplasty. However, it is known that its viability is not always on the ideal level. Various wrapping materials are used to increase the strength of cartilage. Donor site morbidity, which develops following the harvesting of both cartilage and fascia as one such cover material, has attracted interest in recent years. OBJECTIVE: In this study, we aimed to investigate the potential of dermis and tendon autografts as alternatives to fascia and cartilage. MATERIAL AND METHOD: The sample of the study included 16 New Zealand white rabbits. The right auricular cartilage of all rabbits was amputated, and it was transformed into diced cartilage autografts. The dermis autografts from the right gluteal areas of the rabbits were deepithelialized, and lumbosacral fascia autografts were harvested from the same incision. Additionally, the Achilles tendon of each rabbit was harvested and transformed into diced tendon autografts. Four different autografts were embedded under the skin of each rabbit from 4 different pouches opened in the back of the rabbit. These autografts included diced cartilage alone (Intervention 1), fascia-wrapped cartilage (Intervention 2), dermis-wrapped cartilage (Intervention 3) and fascia-wrapped tendon (Intervention 4) autografts. RESULTS: Intervention 1 had the most irregular appearance, the outcomes in Intervention 4 were volumetrically smaller and softer. Connective tissue formed between the diced pieces in all interventions, and it was observed that the dermis and fascia had a capsule-like appearance, and their viability was preserved. The differences between the initial and final measurements of the volumes of interventions 1, 2 and 3 were statistically significant (p < 0.05). There was no significant difference between the initial and final volumetric measurements of intervention 4 (p > 0.05). More peripheral proliferation was observed in the interventions of fascia-wrapped and dermis-wrapped diced cartilage compared to the other interventions. The intervention including fascia-wrapped diced tendon grafts had displayed more fibrosis, fragmentation and collagen fibers, while it showed a lower amount of elastic fiber. There were no significant differences among the intervention in terms of other histological parameters. CONCLUSION: Tendon autografts may be a good option for dorsal augmentation rhinoplasty as they are easily harvested and have minimal donor site morbidity. Dermis autograft usage is more advantageous than fascia usage in terms of accessibility and convenience. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Human Acellular Collagen Matrices-Clinical Opportunities in Tissue Replacement.

The field of regenerative medicine is increasingly in need of effective and biocompatible materials for tissue engineering. Human acellular dermal matrix (hADM)-derived collagen matrices stand out as a particularly promising candidate. Their ability to preserve structural integrity, coupled with exceptional biocompatibility, positions them as a viable choice for tissue replacement. However, their clinical application has been largely confined to serving as scaffolds. This study aims to expand the horizon of clinical uses for collagen sheets by exploring the diverse cutting-edge clinical demands. This review illustrates the clinical utilizations of collagen sheets beyond traditional roles, such as covering skin defects or acting solely as scaffolds. In particular, the potential of Epiflex®, a commercially available and immediately clinically usable allogeneic membrane, will be evaluated. Collagen sheets have demonstrated efficacy in bone reconstruction, where they can substitute the induced Masquelet membrane in a single-stage procedure, proving to be clinically effective and safe. The application of these membranes allow the reconstruction of substantial tissue defects, without requiring extensive plastic reconstructive surgery. Additionally, they are found to be apt for addressing osteochondritis dissecans lesions and for ligament reconstruction in the carpus. The compelling clinical examples showcased in this study affirm that the applications of human ADM extend significantly beyond its initial use for skin defect treatments. hADM has proven to be highly successful and well-tolerated in managing various etiologies of bone and soft tissue defects, enhancing patient care outcomes. In particular, the application from the shelf reduces the need for additional surgery or donor site defects.

Role of Dermal Factors Involved in Regulating the Melanin and Melanogenesis of Mammalian Melanocytes in Normal and Abnormal Skin.

Mammalian melanin is produced in melanocytes and accumulated in melanosomes. Melanogenesis is supported by many factors derived from the surrounding tissue environment, such as the epidermis, dermis, and subcutaneous tissue, in addition to numerous melanogenesis-related genes. The roles of these genes have been fully investigated and the molecular analysis has been performed. Moreover, the role of paracrine factors derived from epidermis has also been studied. However, the role of dermis has not been fully studied. Thus, in this review, dermis-derived factors including soluble and insoluble components were overviewed and discussed in normal and abnormal circumstances. Dermal factors play an important role in the regulation of melanogenesis in the normal and abnormal mammalian skin.

Thioredoxin promotes the regeneration and binding of elastic fibre and basement membrane.

OBJECTIVE: Thioredoxin (TRX), a ubiquitous protein with strong antioxidant activity, decreases in the skin with age. A decrease in TRX is expected to induce cellular senescence, chronic inflammation, and degeneration and loss of extracellular matrix (ECM), such as collagen and elastin within the skin. In this study, we investigated the effects of TRX addition to excised skin or skin models to understand the role of TRX on cells and ECM within the skin. METHODS: To evaluate its effect on skin cells, we cultured a three-dimensional (3D) skin model in a medium containing TRX. The mRNA expression levels of proteins related to elastic and collagen fibres and the basement membrane were determined. Furthermore, 3D imaging and computational analysis were performed to evaluate the effect of TRX on the elastic fibres and extending COL VII structures in excised human skin after coculturing with TRX for 1, 4, 5 and 6 days. RESULTS: Thioredoxin application to a 3D skin model upregulated elastin, COLI and COLVII mRNA expression. Applying TRX to the excised skin increased the number of linear elastic fibres. This effect of TRX demonstrated a daily increment in a dose-dependent manner. Thioredoxin extended the fibrous structure of COL VII into the dermis, expanding its colocalization region with elastic fibres. These structural effects were confirmed using 3D imaging and computational methods. CONCLUSION: Thioredoxin elongates elastic fibres from the dermis to the basement membrane and extends the COL VII structure from the basement membrane to the dermis in excised human skin. These findings suggest the potential of TRX to protect the skin against age-related alterations such as wrinkles and sagging.

OBJECTIF: Thioredoxin (TRX), une protéine ubiquitaire dotée d'une forte activité antioxydante, diminue dans la peau avec l'âge. Une diminution de la TRX est susceptible d'induire la sénescence cellulaire, l'inflammation chronique, et la dégénérescence ainsi que la perte de la matrice extracellulaire (ECM), telle que le collagène et l'élastine de la peau. Dans cette étude, nous avons examiné les effets de l'ajout de TRX à la peau prélevée ou aux modèles de peau afin de comprendre le rôle de TRX sur les cellules et la matrice extracellulaire (ECM) de la peau. MÉTHODES: Pour évaluer son effet sur les cellules cutanées, nous avons cultivé un modèle de peau tridimensionnel (3D) dans un milieu contenant du TRX. Les niveaux d'expression de l'ARNm des protéines liées aux fibres élastiques et de collagène ainsi que de la membrane basale ont été déterminés. De plus, une imagerie 3D et une analyse informatique ont été réalisées pour évaluer l'effet de la TRX sur les fibres élastiques et les structures de COL VII étendues dans la peau humaine prélevée après une coculture avec la TRX pendant 1, 4, 5 et 6 jours. RÉSULTATS: L'application de la Thioredoxin à un modèle de peau en 3D a régulé à la hausse l'expression de l'élastine, du COLI et du COLVII au niveau de l'ARNm. L'application de TRX à la peau excisée a augmenté le nombre de fibres élastiques linéaires. Cet effet du TRX a montré une augmentation quotidienne de manière dose­dépendante. Le Thioredoxin a étendu la structure fibreuse du COL VII dans le derme, élargissant ainsi sa région de colocalisation avec les fibres élastiques. Ces effets structuraux ont été confirmés à l'aide d'imagerie 3D et de méthodes computationnelles. CONCLUSIONS: La Thioredoxin allonge les fibres élastiques du derme à la membrane basale et étend la structure de COL VII de la membrane basale au derme dans la peau humaine excisée. Ces résultats suggèrent le potentiel de la TRX pour protéger la peau contre les altérations liées à l'âge telles que les rides et le relâchement cutané.