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Molecules (Basel, Switzerland) Jul 2022Skin is the largest organ in the body comprised of three different layers including the epidermis, dermis, and hypodermis. The dermis is mainly composed of dermal... (Review)
Review
Skin is the largest organ in the body comprised of three different layers including the epidermis, dermis, and hypodermis. The dermis is mainly composed of dermal fibroblasts and extracellular matrix (ECM), such as collagen and elastin, which are strongly related to skin elasticity and firmness. Skin is continuously exposed to different kinds of environmental stimuli. For example, ultraviolet (UV) radiation, air pollutants, or smoking aggravates skin aging. These external stimuli accelerate the aging process by reactive oxygen species (ROS)-mediated signaling pathways and even cause aging-related diseases. Skin aging is characterized by elasticity loss, wrinkle formation, a reduced dermal-epidermal junction, and delayed wound healing. Thus, many studies have shown that natural polyphenol compounds can delay the aging process by regulating age-related signaling pathways in aged dermal fibroblasts. This review first highlights the relationship between aging and its related molecular mechanisms. Then, we discuss the function and underlying mechanism of various polyphenols for improving skin aging. This study may provide essential insights for developing functional cosmetics and future clinical applications.
Topics: Aged; Aging; Dermis; Fibroblasts; Humans; Polyphenols; Skin; Skin Aging; Ultraviolet Rays
PubMed: 35889225
DOI: 10.3390/molecules27144351 -
Scientific Reports Jan 2024Melasma relapse is almost common after discontinuation of conventional treatment. Recent studies suggesting that photoaging dermis is the main pathomechanism of melasma,...
Melasma relapse is almost common after discontinuation of conventional treatment. Recent studies suggesting that photoaging dermis is the main pathomechanism of melasma, emphasize the dermal targeting therapy. We investigated maintenance effect of microneedling radiofrequency (RF) for melasma treatment. Subjects with melasma were administered oral tranexamic acid and triple combination cream for 2 months and a randomly assigned half face was treated with RF. After discontinuation of conventional therapy, the half face RF continued monthly over 6 months. Modified melasma area severity index (mMASI) score and L* value by a chromameter were collected monthly. Fifteen subjects were enrolled and eleven completed the 8-month study. At 2nd month of conventional therapy, all subjects showed improvement with a 64% reduction in mMASI score. With continuous RF treatment, the improvement was well maintained; whereas in untreated side, the Δ L* gradually decreased, returning to the baseline after the conventional therapy ended. The continuous microneedling RF therapy is beneficial in maintaining the conventional therapy of melasma suggesting the protective effect of dermal targeting therapy in melasma development.(Clinical Trial registration number: NCT05710068, date of first registration: 02/02/2023).
Topics: Humans; Radiofrequency Therapy; Food; Melanosis; Orobanchaceae; Dermis
PubMed: 38200171
DOI: 10.1038/s41598-023-51133-w -
Acta Biomaterialia Oct 2021Severe injuries to skin including hypodermis require full-thickness skin replacement. Here, we bioengineered a tri-layered human skin substitute (TLSS) containing the...
Severe injuries to skin including hypodermis require full-thickness skin replacement. Here, we bioengineered a tri-layered human skin substitute (TLSS) containing the epidermis, dermis, and hypodermis. The hypodermal layer was generated by differentiation of human adipose stem cells (ASC) in a collagen type I hydrogel and combined with a prevascularized dermis consisting of human dermal microvascular endothelial cells and fibroblasts, which arranged into a dense vascular network. Subsequently, keratinocytes were seeded on top to generate the epidermal layer of the TLSS. The differentiation of ASC into adipocytes was confirmed in vitro on the mRNA level by the presence of adiponectin, as well as by the expression of perilipin and FABP-4 proteins. Moreover, functional characteristics of the hypodermis in vitro and in vivo were evaluated by Oil Red O, BODIPY, and AdipoRed stainings visualizing intracellular lipid droplets. Further, we demonstrated that both undifferentiated ASC and mature adipocytes present in the hypodermis influenced the keratinocyte maturation and homeostasis in the skin substitutes after transplantation. In particular, an enhanced secretion of TGF-β1 by these cells affected the epidermal morphogenesis as assessed by the expression of key proteins involved in the epidermal differentiation including cytokeratin 1, 10, 19 and cornified envelope formation such as involucrin. Here, we propose a novel functional hypodermal-dermo-epidermal tri-layered skin substitute containing blood capillaries that efficiently promote regeneration of skin defects. STATEMENT OF SIGNIFICANCE: The main objective of this study was to develop and assess the usefulness of a tri-layered human prevascularized skin substitute (TLSS) containing an epidermis, dermis, and hypodermis. The bioengineered hypodermis was generated from human adipose mesenchymal stem cells (ASC) and combined with a prevascularized dermis and epidermis. The TLSS represents an exceptional model for studying the role of cell-cell and cell-matrix interactions in vitro and in vivo. In particular, we observed that enhanced secretion of TGF-β1 in the hypodermis exerted a profound impact on fibroblast and keratinocyte differentiation, as well as epidermal barrier formation and homeostasis. Therefore, improved understanding of the cell-cell interactions in such a physiological skin model is essential to gain insights into different aspects of wound healing.
Topics: Bioengineering; Dermis; Endothelial Cells; Fibroblasts; Humans; Keratinocytes; Skin; Skin, Artificial; Subcutaneous Tissue; Tissue Engineering
PubMed: 34303011
DOI: 10.1016/j.actbio.2021.07.033 -
Frontiers in Immunology 2020Transcutaneous immunization (TCI) via needle-free and non-invasive drug delivery systems is a promising approach for overcoming the current limitations of conventional... (Review)
Review
Transcutaneous immunization (TCI) via needle-free and non-invasive drug delivery systems is a promising approach for overcoming the current limitations of conventional parenteral vaccination methods. The targeted access to professional antigen-presenting cell (APC) populations within the skin, such as Langerhans cells (LCs), various dermal dendritic cells (dDCs), macrophages, and others makes the skin an ideal vaccination site to specifically shape immune responses as required. The stratum corneum (SC) of the skin is the main penetration barrier that needs to be overcome by the vaccine components in a coordinated way to achieve optimal access to dermal APC populations that induce priming of T-cell or B-cell responses for protective immunity. While there are numerous approaches to penetrating the SC, such as electroporation, sono- or iontophoresis, barrier and ablative methods, jet and powder injectors, and microneedle-mediated transport, we will focus this review on the recent progress made in particle-based systems for TCI. This particular approach delivers vaccine antigens together with adjuvants to perifollicular APCs by diffusion and deposition in hair follicles. Different delivery systems including nanoparticles and lipid-based systems, for example, solid nano-emulsions, and their impact on immune cells and generation of a memory effect are discussed. Moreover, challenges for TCI are addressed, including timely and targeted delivery of antigens and adjuvants to APCs within the skin as well as a deeper understanding of the ill-defined mechanisms leading to the induction of effective memory responses.
Topics: Adjuvants, Immunologic; Administration, Cutaneous; Antigen-Presenting Cells; Dermis; Drug Delivery Systems; Electroporation; Humans; Injections, Jet; Langerhans Cells; Liposomes; Lymph Nodes; Nanoparticles; Ovalbumin; Particle Size; Peptide Fragments; Pharmaceutical Vehicles; Sonication; T-Lymphocytes; Vaccination; Vaccines, Virus-Like Particle
PubMed: 32174915
DOI: 10.3389/fimmu.2020.00266 -
International Journal of Molecular... Aug 2021Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the...
Deep partial-thickness burns damage most of the dermis and can cause severe pain, scarring, and mortality if left untreated. This study serves to evaluate the effectiveness of crosslinked keratin-alginate composite sponges as dermal substitutes for deep partial-thickness burns. Crosslinked keratin-alginate sponges were tested for the ability to support human dermal fibroblasts in vitro and to support the closure and healing of partial-thickness burn wounds in pigs. Keratin-alginate composite sponges supported the enhanced proliferation of human dermal fibroblasts compared to alginate-only sponges and exhibited decreased contraction in vitro when compared to keratin only sponges. As dermal substitutes in vivo, the sponges supported the expression of keratin 14, alpha-smooth muscle actin, and collagen IV within wound sites, comparable to collagen sponges. Keratin-alginate composite sponges supported the regeneration of basement membranes in the wounds more than in collagen-treated wounds and non-grafted controls, suggesting the subsequent development of pathological scar tissues may be minimized. Results from this study indicate that crosslinked keratin-alginate sponges are suitable alternative dermal substitutes for clinical applications in wound healing and skin regeneration.
Topics: Alginates; Animals; Bandages, Hydrocolloid; Burns; Cells, Cultured; Dermis; Humans; Hydrogels; Keratins; Male; Materials Testing; Severity of Illness Index; Skin; Swine; Wound Healing
PubMed: 34445299
DOI: 10.3390/ijms22168594 -
Scientific Reports Oct 2023Oxytocin (OXT) is a neuropeptide hormone termed "love hormone" produced and released during childbirth and lactation. It is also produced in response to skin stimulation...
Oxytocin (OXT) is a neuropeptide hormone termed "love hormone" produced and released during childbirth and lactation. It is also produced in response to skin stimulation (e.g., during hugging and massaging) and music therapy. The effects of OXT on various organs have been revealed in recent years; however, the relationship between hair follicles and OXT remains unclear. In this study, we examined the effects of OXT on dermal papilla (DP) cells that control hair growth by secreting growth/regression signals. Gene expression analysis revealed that DP signature markers were significantly upregulated in DP cells treated with OXT. In addition, we tested the hair growth-promoting effects of OXT using in vitro hair follicle organoids. OXT promoted the growth of hair peg-like sprouting by upregulating the expression of growth-promoting factors, including genes encoding vascular endothelial growth factor A (VEGFA). This study highlights the positive effects of OXT in hair follicles and may assist in the development of new treatments for alopecia.
Topics: Female; Humans; Dermis; Oxytocin; Vascular Endothelial Growth Factor A; Cells, Cultured; Hair Follicle; Hair
PubMed: 37863919
DOI: 10.1038/s41598-023-40521-x -
Nature Jun 2022Proper ectodermal patterning during human development requires previously identified transcription factors such as GATA3 and p63, as well as positional signalling from...
Proper ectodermal patterning during human development requires previously identified transcription factors such as GATA3 and p63, as well as positional signalling from regional mesoderm. However, the mechanism by which ectoderm and mesoderm factors act to stably pattern gene expression and lineage commitment remains unclear. Here we identify the protein Gibbin, encoded by the Xia-Gibbs AT-hook DNA-binding-motif-containing 1 (AHDC1) disease gene, as a key regulator of early epithelial morphogenesis. We find that enhancer- or promoter-bound Gibbin interacts with dozens of sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes. The loss of Gibbin causes an increase in DNA methylation at GATA3-dependent mesodermal genes, resulting in a loss of signalling between developing dermal and epidermal cell types. Notably, Gibbin-mutant human embryonic stem-cell-derived skin organoids lack dermal maturation, resulting in p63-expressing basal cells that possess defective keratinocyte stratification. In vivo chimeric CRISPR mouse mutants reveal a spectrum of Gibbin-dependent developmental patterning defects affecting craniofacial structure, abdominal wall closure and epidermal stratification that mirror patient phenotypes. Our results indicate that the patterning phenotypes seen in Xia-Gibbs and related syndromes derive from abnormal mesoderm maturation as a result of gene-specific DNA methylation decisions.
Topics: Animals; Humans; Mice; Dermis; DNA Methylation; DNA-Binding Proteins; Ectoderm; Embryonic Stem Cells; Epidermal Cells; Epithelial Cells; Epithelium; GATA3 Transcription Factor; Gene Expression Regulation, Developmental; Mesoderm; Morphogenesis; Mutation; Organoids; Trans-Activators; Transcription Factors
PubMed: 35585237
DOI: 10.1038/s41586-022-04727-9 -
Journal of Cellular and Molecular... Jun 2023The skin harbours transcriptionally and functionally heterogeneous mesenchymal cells that participate in various physiological activities by secreting biochemical cues....
The skin harbours transcriptionally and functionally heterogeneous mesenchymal cells that participate in various physiological activities by secreting biochemical cues. In this study, we aimed to identify a new subpopulation of dermal mesenchymal cells that enhance hair follicle regeneration through a paracrine mechanism. Integrated single-cell RNA sequencing (scRNA-seq) data analysis revealed epidermal growth factor receptor (EGFR) as a marker of distinct fibroblast subpopulation in the neonatal murine dermis. Immunofluorescence staining and fluorescence-activated cell sorting (FACS) were used to validate the existence of the cell population in Krt14-rtTA-H2BGFP mouse. The difference of gene expression between separated cell subpopulation was examined by real-time PCR. Potential effect of the designated factor on hair follicle regeneration was observed after the application on excisional wounds in Krt14-rtTA-H2BGFP mouse. Immunofluorescence staining demonstrated the existence of dermal EGFR cells in neonatal and adult mouse dermis. The EGFR mesenchymal population, sorted by FACS, displayed a higher expression level of Igf1 (insulin-like growth factor 1). Co-localisation of IGF1 with EGFR in the mouse dermis and upregulated numbers of hair follicles in healed wounds following the application of exogenous IGF1 illustrated the contribution of EGFR cells in promoting wound-induced hair follicle neogenesis. Our results indicate that EGFR identifies a subpopulation of dermal fibroblasts that contribute to IGF1 promotion of hair follicle neogenesis. It broadens the understanding of heterogeneity and the mesenchymal cell function in skin and may facilitate the potential translational application of these cells.
Topics: Animals; Mice; Dermis; ErbB Receptors; Hair Follicle; Insulin-Like Growth Factor I; Skin
PubMed: 37165726
DOI: 10.1111/jcmm.17766 -
Scientific Reports Jun 2024The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis...
The current investigation aims to study the embryonic dermis formed in the early stages of development and identify the initial interstitial components of the dermis that serve as biological and structural scaffolds for the development of the dermal tissue. To investigate the dermal structure, the current study used morphological and immunological techniques. TCs identified by TEM. They had a cell body and unique podomeres and podoms. They formed a 3D network spread throughout the dermis. Homocellular contact established between them, as well as heterocellular contacts with other cells. Immunohistochemical techniques using specific markers for TCss CD34, CD117, and VEGF confirmed TC identification. TCs represent the major interstitial component in the dermal tissue. They established a 3D network, enclosing other cells and structures. Expression of VEGF by TC promotes angiogenesis. TCs establish cellular contact with sprouting endothelial cells. At the site of cell junction with TCs, cytoskeletal filaments identified and observed to form the pseudopodium core that projects from endothelial cells. TCs had proteolytic properties that expressed MMP-9, CD68, and CD21. Proteolytic activity aids in the removal of components of the extracellular matrix and the phagocytosis of degraded remnants to create spaces to facilitate the development of new dermal structures. In conclusion, TCs organized the scaffold for the development of future dermal structures, including fibrous components and skin appendages. Studying dermal TCs would be interested in the possibility of developing therapeutic strategies for treating different skin disorders and diseases.
Topics: Telocytes; Immunohistochemistry; Dermis; Humans; Antigens, CD34; Animals; Vascular Endothelial Growth Factor A; Antigens, CD; Matrix Metalloproteinase 9; Endothelial Cells; Antigens, Differentiation, Myelomonocytic; CD68 Molecule
PubMed: 38886354
DOI: 10.1038/s41598-024-63802-5 -
International Journal of Molecular... Jun 2021Particulate matter with aerodynamic diameter ≤2.5 μm (PM) increases oxidative stress through free radical generation and incomplete volatilization. In addition to...
Particulate matter with aerodynamic diameter ≤2.5 μm (PM) increases oxidative stress through free radical generation and incomplete volatilization. In addition to affecting the respiratory system, PM causes aging- and inflammation-related damage to skin. Farnesol (Farn), a natural benzyl semiterpene, possesses anti-inflammatory, antioxidative, and antibacterial properties. However, because of its poor water solubility and cytotoxicity at high concentrations, the biomedical applications of Farn have been limited. This study examined the deleterious effects of PM on the epidermis and dermis. In addition, Farn-encapsulated liposomes (Lipo-Farn) and gelatin/HA/xanthan gel containing Lipo-Farn were prepared and applied in vivo to repair and alleviate PM-induced damage and inflammation in skin. The prepared Lipo-Farn was 342 ± 90 nm in diameter with an encapsulation rate of 69%; the encapsulation significantly reduced the cytotoxicity of Farn. Lipo-Farn exhibited a slow-release rate of 35% after 192 h of incubation. The half-maximal inhibitory concentration of PM was approximately 850 μg/mL, and ≥400 μg/mL PM significantly increased IL-6 production in skin fibroblasts. Severe impairment in the epidermis and hair follicles and moderate impairment in the dermis were found in the groups treated with post-PM and continuous subcutaneous injection of PM. Acute and chronic inflammation was observed in the skin in both experimental categories in vivo. Treatment with 4 mM Lipo-Farn largely repaired PM-induced injury in the epidermis and dermis, restored injured hair follicles, and alleviated acute and chronic inflammation induced by PM in rat skin. In addition, treatment with 4 mM pure Farn and 2 mM Lipo-Farn exerted moderate reparative and anti-inflammatory effects on impaired skin. The findings of the current study indicate the therapeutic and protective effects of Lipo-Farn against various injuries caused by PM in the pilosebaceous units, epidermis, and dermis of skin.
Topics: Animals; Antioxidants; Dermis; Epidermis; Farnesol; Female; Liposomes; Particulate Matter; Protective Agents; Rats; Rats, Sprague-Dawley; Skin Diseases
PubMed: 34199947
DOI: 10.3390/ijms22116076