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Journal of Biomedicine & Biotechnology 2011Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing... (Review)
Review
Middle ear acquired cholesteatoma is a pathological condition associated with otitis media, which may be associated with temporal bone resorption, otorrhea and hearing loss, and occasionally various other complications. Cholesteatoma is characterized by the enhanced proliferation of epithelial cells with aberrant morphologic characteristics. Unfortunately, our understanding of the mechanism underlying its pathogenesis is limited. To investigate its pathogenesis, different animal models have been used. This paper provides a brief overview of the current status of research in the field of pathogenesis of middle ear acquired cholesteatoma, four types of animal models previously reported on, up-to-date cholesteatoma research using these animal models, our current studies of the local hybrid ear model, and the future prospect of new animal models of middle ear cholesteatoma.
Topics: Animals; Cholesteatoma, Middle Ear; Dermis; Disease Models, Animal; Ear, Middle; Implants, Experimental
PubMed: 21541229
DOI: 10.1155/2011/394241 -
The Journal of Investigative Dermatology Apr 2021As a barrier organ, the skin is an ideal model to study environmentally-induced (extrinsic) aging. In this review, we explain the development of extrinsic skin aging as... (Review)
Review
As a barrier organ, the skin is an ideal model to study environmentally-induced (extrinsic) aging. In this review, we explain the development of extrinsic skin aging as a consequence of skin exposure to specific exposomal factors, their interaction with each other, and the modification of their effects on the skin by genetic factors. We also review the evidence that exposure to these exposomal factors causes extrinsic skin aging by mechanisms that critically involve the accumulation of macromolecular damage and the subsequent development of functionally altered and/or senescent fibroblasts in the dermal compartment of the skin.
Topics: Air Pollutants; Cellular Senescence; DNA Damage; Dermis; Environmental Exposure; Fibroblasts; Humans; Skin Aging; Ultraviolet Rays
PubMed: 33541724
DOI: 10.1016/j.jid.2020.12.011 -
The International Journal of... Mar 2012One unique physiological characteristic of frogs is that their main route for intake of water is across the skin. In these animals, the skin acts in concert with the... (Review)
Review
One unique physiological characteristic of frogs is that their main route for intake of water is across the skin. In these animals, the skin acts in concert with the kidney and urinary bladder to maintain electrolyte homeostasis. Water absorption across the skin is driven by the osmotic gradient that develops as a consequence of solute transport. Our recent study demonstrated that chytridiomycosis, an infection of amphibian skin by the fungal pathogen, Batrachochytrium dendrobatidis, inhibits epithelial Na(+) channels, attenuating Na(+) absorption through the skin. In frogs that become severely affected by this fungus, systemic depletion of Na(+), K(+) and Cl(-) is thought to cause deterioration of cardiac electrical function, leading to cardiac arrest. Here we review the ion transport mechanisms of frog skin, and discuss the effect of chytridiomycosis on these mechanisms.
Topics: Animals; Anura; Biological Transport; Chytridiomycota; Dermis; Electrolytes; Epidermis; Skin; Sodium Channels; Water-Electrolyte Balance
PubMed: 22182598
DOI: 10.1016/j.biocel.2011.12.002 -
Scientific Reports Jun 2021The skin barrier is provided by the organized multi-layer structure of epidermal cells, which is dynamically maintained by a continuous supply of cells from the basal...
The skin barrier is provided by the organized multi-layer structure of epidermal cells, which is dynamically maintained by a continuous supply of cells from the basal layer. The epidermal homeostasis can be disrupted by various skin diseases, which often cause morphological changes not only in the epidermis but in the dermis. We present a three-dimensional agent-based computational model of the epidermis that takes into account the deformability of the dermis. Our model can produce a stable epidermal structure with well-organized layers. We show that its stability depends on the cell supply rate from the basal layer. Modeling the morphological change of the dermis also enables us to investigate how the stiffness of the dermis affects the structure and barrier functions of the epidermis. Besides, we show that our model can simulate the formation of a corn (clavus) by assuming hyperproliferation and rapid differentiation. We also provide experimental data for human corn, which supports the model assumptions and the simulation result.
Topics: Computer Simulation; Dermis; Epidermis; Homeostasis; Humans; Skin Diseases
PubMed: 34168195
DOI: 10.1038/s41598-021-92540-1 -
Oncotarget Apr 2017To explore the profibrotic characteristics of the autografted dermis, acellular dermal matrix, and dermal fibroblasts from superficial/deep layers of pig skin, 93 wounds...
To explore the profibrotic characteristics of the autografted dermis, acellular dermal matrix, and dermal fibroblasts from superficial/deep layers of pig skin, 93 wounds were established on the dorsa of 7 pigs. 72 wounds autografted with the superficial/deep dermis and acellular dermal matrix served as the superficial/deep dermis and acellular dermal matrix group, respectively, and were sampled at 2, 4, and 8 weeks post-wounding. 21 wounds autografted with/without superficial/deep dermal fibroblasts served as the superficial/deep dermal fibroblast group and the control group, respectively, and were sampled at 2 weeks post-wounding. The hematoxylin and eosin staining showed that the wounded skin thicknesses in the deep dermis group (superficial acellular dermal matrix group) were significantly greater than those in the superficial dermis group (deep acellular dermal matrix group) at each time point, the thickness of the cutting plane in the deep dermal fibroblast group was significantly greater than that in the superficial dermal fibroblast group and the control group. The western blots showed that the α-smooth muscle actin expression in the deep dermis group (superficial acellular dermal matrix group) was significantly greater than that in the superficial dermis group (deep acellular dermal matrix group) at each time point. In summary, the deep dermis and dermal fibroblasts exhibited more profibrotic characteristics than the superficial ones, on the contrary, the deep acellular dermal matrix exhibited less profibrotic characteristics than the superficial one.
Topics: Acellular Dermis; Actins; Animals; Blotting, Western; Cells, Cultured; Cicatrix, Hypertrophic; Dermis; Disease Models, Animal; Female; Fibroblasts; Fibrosis; Humans; Muscle, Smooth; Skin; Skin Transplantation; Swine; Time Factors; Transplantation, Autologous; Wound Healing
PubMed: 28423561
DOI: 10.18632/oncotarget.15389 -
Journal of Virology Feb 2022Herpes simplex virus 1 (HSV-1) invades its human host via the skin and mucosa and initiates infection in the epithelium. While human and murine epidermis are highly... (Comparative Study)
Comparative Study
Herpes simplex virus 1 (HSV-1) invades its human host via the skin and mucosa and initiates infection in the epithelium. While human and murine epidermis are highly susceptible to HSV-1, we recently observed rare infected cells in the human dermis and only minor infection efficiency in murine dermis upon infection. Here, we investigated why cells in the dermis are so inefficiently infected and explored potential differences between murine and human dermal fibroblasts. In principle, primary fibroblasts are highly susceptible to HSV-1; however, we found a delayed infection onset in human compared to murine cells. Intriguingly, only a minor delayed onset of infection was evident in collagen-embedded compared to unembedded human fibroblasts, although expression of the receptor nectin-1 dropped after collagen embedding. This finding is in contrast to previous observations with murine fibroblasts where collagen embedding delayed infection. The application of latex beads revealed limited penetration in the dermis, which was more pronounced in the human than in the murine dermis, supporting the species-specific differences already observed for HSV-1 invasion. Our results suggest that the distinct organization of human and murine dermis contributes to the presence and accessibility of the HSV-1 receptors as well as to the variable barrier function of the extracellular matrix. These contributions, in turn, give rise to inefficient viral access to cells in the dermis while dermal fibroblasts in culture are well infected. Dermal fibroblasts are exposed to HSV-1 upon invasion in skin during infection. Thus, fibroblasts represent a widely used experimental tool to understand virus-host cell interactions and are highly susceptible in culture. The spectrum of fibroblasts' characteristics in their environment, however, clearly differs from the observations under cell culture conditions, implying putative variations in virus-cell interactions. This becomes evident when infection studies in murine as well as human dermis revealed the rather inefficient penetration of HSV-1 in the tissue and uptake in the dermal fibroblasts. Here, we initiated studies to explore the contributions of receptor presence and accessibility to efficient infection of dermal fibroblasts. Our results strengthen the heterogeneity of murine and human dermis and imply that the interplay between dermal barrier function and receptor presence determine how well HSV-1 penetrates the dermis.
Topics: Animals; Collagen; Dermis; Extracellular Matrix; Fibroblasts; Herpesvirus 1, Human; Humans; Mice; Nectins; Species Specificity; Virus Internalization
PubMed: 34908440
DOI: 10.1128/JVI.02068-21 -
The Journal of Investigative Dermatology Sep 2022Clinical application of mechanical stretching is a reconstructive method for skin repair. Although studies have reported dermal fibroblast heterogeneity, whether...
Clinical application of mechanical stretching is a reconstructive method for skin repair. Although studies have reported dermal fibroblast heterogeneity, whether stretching affects individual fibroblast subpopulations equally remains unclear. In this study, we show the changes in dermal structure and papillary fibroblast (Fp) in regenerated human skin. Exhausted skin regeneration caused dermal‒epidermal junction flattening, papillary dermis thinning, and an increase in type III collagen-to-type I collagen ratio, with upregulated hallmarks of aging. Well-regenerated skin displayed a notable increase in the Fp population. Consistent changes were observed in the rat expansion model. Moreover, we found that TGFβ1 expression was especially increased in skin showing good regeneration. Activation of the TGFβ1/SMAD2/3 pathway improved exhausted skin regeneration and resulted in increased collagen content and Fp proliferation, whereas pharmacological inhibition of TGFβ1 action impacted well-regenerated skin. Short-term mechanical stretching that promoted skin regeneration enhanced Fp proliferation, extracellular matrix synthesis, and increased TGFβ1 expression, leading to good regeneration. Conversely, long-term stretching induced premature Fp senescence, leading to poor regeneration. This work shows the mechanism of mechanical stretching in well-skin regeneration that enhances Fp proliferation and extracellular matrix synthesis through the TGFβ1/SMAD2/3 pathway and highlights a crucial role of Fps in stretching-induced skin regeneration.
Topics: Animals; Dermis; Extracellular Matrix; Fibroblasts; Humans; Rats; Regeneration; Skin
PubMed: 35181299
DOI: 10.1016/j.jid.2021.11.043 -
Developmental Biology Nov 2019Salamanders are capable of full-thickness skin regeneration where removal of epidermis, dermis and hypodermis results in scar-free repair. What remains unclear is...
Salamanders are capable of full-thickness skin regeneration where removal of epidermis, dermis and hypodermis results in scar-free repair. What remains unclear is whether regeneration of these tissues recapitulates the cellular events of skin development or occurs through a process unique to regenerative healing. Unfortunately, information on the post-embryonic development of salamander skin is severely lacking, having focused on compartments or cell types, but never on the skin as a complete organ. By examining coordinated development of the epidermis and dermis in axolotls we establish six distinct stages of skin development (I-VI): I-V for normally paedomorphic adults and a sixth stage following metamorphosis. Raising animals either in isolation (zero density pressure) or in groups (density pressure) we find that skin development progresses as a function of animal size and that density directly effects developmental rate. Using keratins, p63, and proliferative markers, we show that when the dermis transforms into the stratum spongiosum and stratum compactum, keratinocytes differentiate into at least three distinct phenotypes that reveal a cryptic stratification program uncoupled from metamorphosis. Lastly, comparing skin regeneration to skin development, we find that dermal regeneration occurs through a unique process, relying heavily on remodeling of the wound extracellular matrix, rather than proceeding through direct development of a dermal lamella produced by the epidermis. By preventing fibroblast influx into the wound bed using beryllium nitrate, we show that in the absence of fibroblast generated ECM production skin regeneration occurs through an alternate route that recapitulates development.
Topics: Ambystoma mexicanum; Animals; Dermis; Embryonic Development; Epidermis; Extracellular Matrix; Fibroblasts; Keratinocytes; Keratins; Male; Regeneration; Signal Transduction; Skin; Time Factors; Wound Healing
PubMed: 31279726
DOI: 10.1016/j.ydbio.2019.07.001 -
Biomedical Materials (Bristol, England) Apr 2016Gene electrotransfer (GET) is a proven and valuable tool for in vivo gene delivery to a variety of tissues such as skin, cardiac muscle, skeletal muscle, and tumors,...
Gene electrotransfer (GET) is a proven and valuable tool for in vivo gene delivery to a variety of tissues such as skin, cardiac muscle, skeletal muscle, and tumors, with controllable gene delivery and expression levels. Optimizing gene expression is a challenging hurdle in preclinical studies, particularly for skin indications, due to differences in electrical conductivity of animal compared to human dermis. Therefore, the goal of this study was to develop an ex vivo model for GET using recellularized human dermis to more closely mimic human skin. Decellularized human dermis (DermACELL(®)) was cultured with human dermal fibroblasts and keratinocytes for 4 weeks. After one week of fibroblast culture, fibroblasts infiltrated and dispersed throughout the dermis. Air-liquid interface culture led to epithelial cell proliferation, stratification and terminal differentiation with distinct basal, spinous, granular and cornified strata. Firefly luciferase expression kinetics were evaluated after GET of recellularized constructs for testing gene delivery parameters to skin in vitro. Elevated luciferase expression persisted up to a week following GET compared to controls without electrotransfer. In summary, recellularized dermis structurally and functionally resembled native human skin in tissue histological organization and homeostasis, proving an effective 3D human skin model for preclinical gene delivery studies.
Topics: Animals; Cell Line; Cell Proliferation; Cells, Cultured; Dermis; Epidermal Cells; Fibroblasts; Gene Transfer Techniques; Humans; Keratinocytes; Male; Skin, Artificial; Tissue Engineering
PubMed: 27121769
DOI: 10.1088/1748-6041/11/3/035002 -
Dermatologic Clinics Jan 2010The laminins are a secreted family of heterotrimeric molecules essential for basement membrane formation, structure, and function. It is now well established that the... (Review)
Review
The laminins are a secreted family of heterotrimeric molecules essential for basement membrane formation, structure, and function. It is now well established that the alpha3 subunit of laminins-332, -321, and -311 plays an important role in mediating epidermal-dermal integrity and is essential for the skin to withstand mechanical stresses. These laminins also regulate cell migration and mechanosignal transduction. This article provides an overview of the gene, transcripts, and protein structures of laminin alpha3. Also discussed are the proposed functions for the alpha3 subunit-containing laminins.
Topics: Cell Adhesion; Cell Movement; Dermis; Desmosomes; Epidermal Cells; Epidermis; Humans; Laminin
PubMed: 19945619
DOI: 10.1016/j.det.2009.10.009