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Science (New York, N.Y.) Nov 2014The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by... (Review)
Review
The skin is our largest sensory organ, transmitting pain, temperature, itch, and touch information to the central nervous system. Touch sensations are conveyed by distinct combinations of mechanosensory end organs and the low-threshold mechanoreceptors (LTMRs) that innervate them. Here we explore the various structures underlying the diverse functions of cutaneous LTMR end organs. Beyond anchoring of LTMRs to the surrounding dermis and epidermis, recent evidence suggests that the non-neuronal components of end organs play an active role in signaling to LTMRs and may physically gate force-sensitive channels in these receptors. Combined with LTMR intrinsic properties, the balance of these factors comprises the response properties of mechanosensory neurons and, thus, the neural encoding of touch.
Topics: Animals; Dermis; Epidermis; Hair; Hair Follicle; Humans; Mechanoreceptors; Mechanotransduction, Cellular; Merkel Cells; Neurons; Pacinian Corpuscles; Touch
PubMed: 25414303
DOI: 10.1126/science.1254229 -
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 -
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 -
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 -
European Journal of Medical Research Feb 2016Over the past 60 years, hyaluronidase has been successfully utilized in ophthalmic surgery and is now being implemented in dermatosurgery as well as in other surgical... (Review)
Review
Over the past 60 years, hyaluronidase has been successfully utilized in ophthalmic surgery and is now being implemented in dermatosurgery as well as in other surgical disciplines. The enzyme is considered a "spreading factor" as it decomplexes hyaluronic acid (also called hyaluronan, HA), an essential component of the extracellular matrix (ECM). When applied as an adjuvant, hyaluronidase enhances the diffusion capacity and bioavailability of injected drugs. Therefore, the enzyme has been used as a local adjuvant to increase the diffusion capacity of local anesthetics, increasing the analgesic efficacy, and the anesthetized area particularly in the first minutes following injection, resulting in diminished intra- and postoperative pain. In aesthetic medicine, the off-label use of hyaluronidase is considered the gold standard for the management of HA-filler-associated complications. Here, we review the clinical use, underlying biological mechanisms, and future directions for the application of hyaluronidase in surgical and aesthetic medicine.
Topics: Anesthetics, Local; Biological Availability; Dermatologic Surgical Procedures; Dermis; Diffusion; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Models, Biological; Ophthalmologic Surgical Procedures
PubMed: 26873038
DOI: 10.1186/s40001-016-0201-5 -
The Journal of Pathology Mar 2021The dermis has disparate embryonic origins; abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm and facial dermis from neural...
The dermis has disparate embryonic origins; abdominal dermis develops from lateral plate mesoderm, dorsal dermis from paraxial mesoderm and facial dermis from neural crest. However, the cell and molecular differences and their functional implications have not been described. We hypothesise that the embryonic origin of the dermis underpins regional characteristics of skin, including its response to wounding. We have compared abdomen, back and cheek, three anatomical sites representing the distinct embryonic tissues from which the dermis can arise, during homeostasis and wound repair using RNA sequencing, histology and fibroblast cultures. Our transcriptional analyses demonstrate differences between body sites that reflect their diverse origins. Moreover, we report histological and transcriptional variations during a wound response, including site differences in ECM composition, cell migration and proliferation, and re-enactment of distinct developmental programmes. These findings reveal profound regional variation in the mechanisms of tissue repair. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Animals; Dermis; Homeostasis; Mice; Wound Healing
PubMed: 33197044
DOI: 10.1002/path.5589 -
The International Journal of... 2004The feather is a complex epidermal organ with hierarchical branches and represents a multi-layered topological transformation of keratinocyte sheets. Feathers are made... (Review)
Review
The feather is a complex epidermal organ with hierarchical branches and represents a multi-layered topological transformation of keratinocyte sheets. Feathers are made in feather follicles. The basics of feather morphogenesis were previously described (Lucas and Stettenheim, 1972). Here we review new molecular and cellular data. After feather buds form (Jiang et al., this issue), they invaginate into the dermis to form feather follicles. Above the dermal papilla is the proliferating epidermal collar. Distal to it is the ramogenic zone where the epidermal cylinder starts to differentiate into barb ridges or rachidial ridge. These neoptile feathers tend to be downy and radially symmetrical. They are replaced by teleoptile feathers which tend to be bilateral symmetrical and more diverse in shapes. We have recently developed a "transgenic feather" protocol that allows molecular analyses: BMPs enhance the size of the rachis, Noggin increases branching, while anti- SHH causes webbed branches. Different feather types formed during evolution (Wu et al., this issue). Pigment patterns along the body axis or intra-feather add more colorful distinctions. These patterns help facilitate the analysis of melanocyte behavior. Feather follicles have to be connected with muscles and nerve fibers, so they can be integrated into the physiology of the whole organism. Feathers, similarly to hairs, have the extraordinary ability to go through molting cycles and regenerate. Some work has been done and feather follicles might serve as a model for stem cell research. Feather phenotypes can be modulated by sex hormones and can help elucidate mechanisms of sex hormone-dependent growth control. Thus, the developmental biology of feather follicles provides a multi-dimension research paradigm that links molecular activities and cellular behaviors to functional morphology at the organismal level.
Topics: Animals; Biological Evolution; Bone Morphogenetic Proteins; Carrier Proteins; Cell Differentiation; Cell Division; Chick Embryo; Dermis; Epidermal Cells; Epidermis; Feathers; Gonadal Steroid Hormones; Hedgehog Proteins; Keratinocytes; Melanocytes; Models, Biological; Morphogenesis; Pigments, Biological; Proteins; Sex Factors; Trans-Activators
PubMed: 15272383
DOI: 10.1387/ijdb.031776my -
The International Journal of... 2004Skin morphogenesis occurs following a continuous series of cell-cell interactions which can be subdivided into three main stages: 1- the formation of a dense dermis and... (Review)
Review
Skin morphogenesis occurs following a continuous series of cell-cell interactions which can be subdivided into three main stages: 1- the formation of a dense dermis and its overlying epidermis in the future appendage fields (macropattern); 2- the organization of these primary homogeneous fields into heterogeneous ones by the appearance of cutaneous appendage primordia (micropattern) and 3- cutaneous appendage organogenesis itself. In this review, we will first show, by synthesizing novel and previously published data from our laboratory, how heterogenetic and heterospecific dermal/epidermal recombinations have allowed us to distinguish between the respective roles of the dermis and the epidermis. We will then summarize what is known from the work of many different research groups about the molecular signaling which mediates these interactions in order to introduce the following articles of this Special Issue and to highlight what remains to done.
Topics: Animals; Dermis; Embryonic Induction; Epidermal Cells; Epidermis; Feathers; Models, Biological; Morphogenesis; Mutation; Organ Culture Techniques; Signal Transduction; Skin; Vertebrates
PubMed: 15272376
DOI: 10.1387/ijdb.15272376 -
Journal of Biomedical Optics Sep 2018The use of multiphoton imaging has become a standard technique to visualize the dermis fibers as it requires no specific staining. The density and organization of...
The use of multiphoton imaging has become a standard technique to visualize the dermis fibers as it requires no specific staining. The density and organization of collagen and elastin are common markers of skin intrinsic aging and photoaging; thus, there is a need of grading this skin aging with quantitative indicators able to provide a robust evaluation of the dermis fibers' state. We propose a systematic analysis of multiphoton images of skin biopsies taken on the buttock and the forearm of patients of different ages. The intensity histograms of images were analyzed through their moments, a wavelet decomposition was done, and the wavelet coefficients distribution was fitted by a generalized Gaussian distribution. Different parameters relative to the collagen or elastin densities, organizations, and structures were calculated and exhibit phenomena specific to intrinsic or extrinsic aging. Those indicators could become a standard method to analyze the degree of skin aging (intrinsic or extrinsic) through multiphoton imaging.
Topics: Adult; Collagen; Dermis; Elastin; Humans; Image Processing, Computer-Assisted; Microscopy, Fluorescence, Multiphoton; Middle Aged; Signal Processing, Computer-Assisted; Skin Aging; Young Adult
PubMed: 30244547
DOI: 10.1117/1.JBO.23.9.096501 -
International Journal of Molecular... Dec 2017Zinc (Zn), which is an essential trace element, is involved in numerous mammalian physiological events; therefore, either a deficiency or excess of Zn impairs cellular... (Review)
Review
Zinc (Zn), which is an essential trace element, is involved in numerous mammalian physiological events; therefore, either a deficiency or excess of Zn impairs cellular machineries and influences physiological events, such as systemic growth, bone homeostasis, skin formation, immune responses, endocrine function, and neuronal function. Zn transporters are thought to mainly contribute to Zn homeostasis within cells and in the whole body. Recent genetic, cellular, and molecular studies of Zn transporters highlight the dynamic role of Zn as a signaling mediator linking several cellular events and signaling pathways. Dysfunction in Zn transporters causes various diseases. This review aims to provide an update of Zn transporters and Zn signaling studies and discusses the remaining questions and future directions by focusing on recent progress in determining the roles of SLC39A/ZIP family members in vivo.
Topics: Animals; B-Lymphocytes; Carrier Proteins; Cation Transport Proteins; Dermis; Humans; Intestinal Mucosa; Signal Transduction; Zinc
PubMed: 29236063
DOI: 10.3390/ijms18122708