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Dermatologic Clinics Jan 2017Human skin wounds heal largely by reparative wound healing rather than regenerative wound healing. Human skin wounds heal with scarring and without pilosebaceous units... (Review)
Review
Human skin wounds heal largely by reparative wound healing rather than regenerative wound healing. Human skin wounds heal with scarring and without pilosebaceous units or other appendages. Dermal fibroblasts come from 2 distinct lineages of cells that have distinct cell markers and, more importantly, distinct functional abilities. Human skin wound healing largely involves the dermal fibroblast lineage from the reticular dermis and not the papillary dermis. If scientists could find a way to stimulate the dermal fibroblast lineages from the papillary dermis in early wound healing, perhaps human skin wounds could heal without scarring and with skin appendages.
Topics: Cicatrix; Dermis; Fibroblasts; Hair Follicle; Humans; Regeneration; Sebaceous Glands; Skin; Sweat Glands; Wound Healing
PubMed: 27890241
DOI: 10.1016/j.det.2016.07.004 -
Skin Research and Technology : Official... May 2019Skin aging is a complex biological process mixing intrinsic and extrinsic factors, such as sun exposure. At the molecular level, skin aging affects in particular the...
BACKGROUND
Skin aging is a complex biological process mixing intrinsic and extrinsic factors, such as sun exposure. At the molecular level, skin aging affects in particular the extracellular matrix proteins.
MATERIALS AND METHODS
Using Raman imaging, which is a nondestructive approach appropriate for studying biological samples, we analyzed how aging modifies the matrix proteins of the papillary and reticular dermis. Biopsies from the buttock and dorsal forearm of volunteers younger than 30 and older than 60 were analyzed in order to identify chronological and photoaging processes. Analyses were performed on skin section, and Raman spectra were acquired separately on the different dermal layers.
RESULTS
We observed differences in dermal matrix structure and hydration state with skin aging. Chronological aging alters in particular the collagen of the papillary dermis, while photoaging causes a decrease in collagen stability by altering proline and hydroxyproline residues in the reticular dermis. Moreover, chronological aging alters glycosaminoglycan content in both dermal compartments.
CONCLUSION
Alterations of the papillary and reticular dermal matrix structures during photo- and chronological aging were clearly depicted by Raman spectroscopy.
Topics: Adult; Aging; Biopsy; Buttocks; Dermis; Female; Forearm; Glycosaminoglycans; Humans; Middle Aged; Skin Aging; Spectrum Analysis, Raman; Young Adult
PubMed: 30402919
DOI: 10.1111/srt.12643 -
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 -
Ultrasound in Medicine & Biology Apr 2022This study investigated the ability of in vivo quantitative ultrasound (QUS) assessment to evaluate lymphedema severity compared with the gold standard method, the...
This study investigated the ability of in vivo quantitative ultrasound (QUS) assessment to evaluate lymphedema severity compared with the gold standard method, the International Society of Lymphology (ISL) stage. Ultrasonic measurements were made around the middle thigh (n = 150). Radiofrequency data were acquired using a clinical scanner and 8-MHz linear probe. Envelope statistical analysis was performed using constant false alarm rate processing and homodyned K (HK) distribution. The attenuation coefficient was calculated using the spectral log-difference technique. The backscatter coefficient (BSC) was obtained by the reference phantom method with attenuation compensation according to the attenuation coefficients in the dermis and hypodermis, and then effective scatterer diameter (ESD) and effective acoustic concentration (EAC) were estimated with a Gaussian model. Receiver operating characteristic curves of QUS parameters were obtained using a linear regression model. A single QUS parameter with high area under the curve (AUC) differed between the dermis (ESD and EAC) and hypodermis (HK) parameters. The combinations with ESD and EAC in the dermis, HK parameters in the hypodermis and typical features (dermal thickness and echogenic regions in the hypodermis) improved classification performance between ISL stages 0 and ≥I (AUC = 0.90 with sensitivity of 75% and specificity of 91%) in comparison with ESD and EAC in the dermis (AUC = 0.82) and HK parameters in the hypodermis (AUC = 0.82). In vivo QUS assessment by BSC and envelope statistical analyses can be valuable for non-invasively classifying an extremely early stage of lymphedema, such as ISL stage I, and following its progression.
Topics: Dermis; Humans; Lymphedema; Phantoms, Imaging; Subcutaneous Tissue; Ultrasonography
PubMed: 35033402
DOI: 10.1016/j.ultrasmedbio.2021.12.003 -
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 -
Experimental Dermatology Jan 2021Tissue homeostasis is maintained through constant, dynamic and heterogeneous communication between cells and their microenvironment. Proteins that are at the same time... (Review)
Review
Tissue homeostasis is maintained through constant, dynamic and heterogeneous communication between cells and their microenvironment. Proteins that are at the same time active at the intracellular, cell periphery and deeper extracellular levels possess the ability to, on the individual molecular level, influence the cells and their microenvironment in a bidirectional manner. The transmembrane collagens are a family of such proteins, which are of notable interest for tissue development and homeostasis. In skin, expression of all transmembrane collagens has been reported and deficiency of transmembrane collagen XVII manifests with distinct skin phenotypes. Nevertheless, transmembrane collagens in skin remain understudied despite the association of them with epidermal wound healing and dermal fibrotic processes. Here, we present an overview of transmembrane collagens and put a spotlight on them as regulators of epidermal-dermal communication and as potential players in fibrinogenesis.
Topics: Cell Communication; Cellular Microenvironment; Collagen; Dermis; Epidermis; Fibroblasts; Fibrosis; Homeostasis; Humans; Skin
PubMed: 32869371
DOI: 10.1111/exd.14180 -
Burns : Journal of the International... Sep 2015Stimulation of α1-adrenoceptors evokes inflammatory cytokine production, boosts neurogenic inflammation and pain, and influences cellular migration and proliferation....
Stimulation of α1-adrenoceptors evokes inflammatory cytokine production, boosts neurogenic inflammation and pain, and influences cellular migration and proliferation. As expression of α1-adrenoceptors increases on dermal nerves and keratinocytes after peripheral nerve injury, the aim of this study was to determine whether another form of tissue injury (a cutaneous burn) triggered a similar response. In particular, changes in expression of α1-adrenoceptors were investigated on dermal nerve fibres, keratinocytes and fibroblast-like cells using immunohistochemistry 2-12 weeks after a full thickness burn in Wistar rats. Within two weeks of the burn, local increases in α1-adrenoceptor expression were seen in the re-forming epidermis, in dense bands of spindle-shaped cells in the upper dermis (putatively infiltrating immune cells and fibroblasts), and on nerve fibres in the deep dermis. In addition, nerve fibre density increased approximately three-fold in the deep dermis, and this response persisted for several more weeks. In contrast, α1-adrenoceptor labelled cells and staining intensity in the upper dermis decreased contralateral to the burn, as did nerve fibre density in the deep dermis. These findings suggest that inflammatory mediators and/or growth factors at the site of a burn trigger the synthesis of α1-adrenoceptors on resident epidermal cells and nerve fibres, and an influx of α1-adrenoceptor labelled cells. The heightened expression of α1-adrenoceptors in injured tissue could shape inflammatory and wound healing responses.
Topics: Animals; Burns; Dermis; Epidermal Cells; Epidermis; Fibroblasts; Immunohistochemistry; Keratinocytes; Peripheral Nerves; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Skin; Up-Regulation
PubMed: 25630693
DOI: 10.1016/j.burns.2014.12.015 -
The Journal of Dermatology Jun 2017
Topics: Adult; Dermis; Dermoscopy; Female; Fingers; Humans; Neoplasms, Fibroepithelial; Skin Neoplasms
PubMed: 28150336
DOI: 10.1111/1346-8138.13745 -
Burns : Journal of the International... Jun 2016
Topics: Burns; Dermis; Epidermis; Humans; Terminology as Topic; Trauma Severity Indices
PubMed: 26818957
DOI: 10.1016/j.burns.2016.01.003 -
Development, Growth & Differentiation Aug 2018Adult mammals do not regenerate the dermis of the skin but form a scar after a deep skin injury. Since a scar causes serious medical problems, skin regeneration, instead... (Review)
Review
Adult mammals do not regenerate the dermis of the skin but form a scar after a deep skin injury. Since a scar causes serious medical problems, skin regeneration, instead of formation of a scar, has been strongly desired from a clinical point of view. Recent studies have suggested multiple origins of myofibroblasts, which are scar-forming cells in skin wound healing of mammals. While amphibians have skin structures that are basically common to mammals as tetrapods, both urodele and anuran amphibians regenerate almost complete skin structures including the dermis and secretion glands without forming a remarkable scar after a deep skin injury. In skin regeneration of a metamorphosed Xenopus laevis, an amphibian, cells that resemble limb blastema cells accumulate under the epidermis after injury and cells from subcutaneous tissues (tissues underlying the skin) contribute to skin regeneration. The skin of urodele amphibians and that of anuran amphibians provide valuable models for studying skin regeneration as adults. Recent progress in transgenesis and genome editing techniques with whole genome sequencing in Xenopus and an axolotl have enabled comparative analyses by molecular genetics of mammal skin and amphibian skin. Such comparative analyses would enable direct comparison of scar-forming myofibroblasts in mammals and blastema-like cells that contribute to skin regeneration in amphibians, ultimately leading to realization of skin regeneration in adult mammals. Amphibian skin regeneration will also be useful for determining how to step up skin regeneration to a higher level of regeneration such as limb regeneration in the future.
Topics: Adult; Ambystoma mexicanum; Animals; Cicatrix; Dermis; Disease Models, Animal; Humans; Myofibroblasts; Regeneration; Xenopus laevis
PubMed: 29947057
DOI: 10.1111/dgd.12544