► An update of the molecular basis of different keratin-related genodermatoses is presented. ► Clinical emphasis is made on epidermolysis bullosa simplex and keratinopathic ichthyosis. ► Currently ...available and emerging model tools for prognostic future treatments are emphasized. ► Detailed molecular dissection of the disease mechanisms could lead to novel therapies.
Keratins, the major structural protein of all epithelia are a diverse group of cytoskeletal scaffolding proteins that form intermediate filament networks, providing structural support to keratinocytes that maintain the integrity of the skin. Expression of keratin genes is usually regulated by differentiation of the epidermal cells within the stratifying squamous epithelium. Amongst the 54 known functional keratin genes in humans, about 22 different genes including, the cornea, hair and hair follicle-specific keratins have been implicated in a wide range of hereditary diseases. The exact phenotype of each disease usually reflects the spatial expression level and the types of mutated keratin genes, the location of the mutations and their consequences at sub-cellular levels as well as other epigenetic and/or environmental factors. The identification of specific pathogenic mutations in keratin disorders formed the basis of our understanding that led to re-classification, improved diagnosis with prognostic implications, prenatal testing and genetic counseling in severe keratin genodermatoses. Molecular defects in cutaneous keratin genes encoding for keratin intermediate filaments (KIFs) causes keratinocytes and tissue-specific fragility, accounting for a large number of genetic disorders in human skin and its appendages. These diseases are characterized by keratinocytes fragility (cytolysis), intra-epidermal blistering, hyperkeratosis, and keratin filament aggregation in severely affected tissues. Examples include epidermolysis bullosa simplex (EBS; K5, K14), keratinopathic ichthyosis (KPI; K1, K2, K10) i.e. epidermolytic ichthyosis (EI; K1, K10) and ichthyosis bullosa of Siemens (IBS; K2), pachyonychia congenita (PC; K6a, K6b, K16, K17), epidermolytic palmo-plantar keratoderma (EPPK; K9, (K1)), monilethrix (K81, K83, K86), ectodermal dysplasia (ED; K85) and steatocystoma multiplex. These keratins also have been identified to have roles in apoptosis, cell proliferation, wound healing, tissue polarity and remodeling. This review summarizes and discusses the clinical, ultrastructural, molecular genetics and biochemical characteristics of a broad spectrum of keratin-related genodermatoses, with special clinical emphasis on EBS, EI and PC. We also highlight current and emerging model tools for prognostic future therapies. Hopefully, disease modeling and in-depth understanding of the molecular pathogenesis of the diseases may lead to the development of novel therapies for several hereditary cutaneous diseases.
The feather aerofoil is unequalled in nature. It is comprised of a central rachis, serial paired branches or barbs, from which arise further branches, the barbules. Barbs and barbules arise from the ...significantly thinner lateral walls (the epicortex) of the rachis and barbs respectively, as opposed to the thicker dorsal and ventral walls (the cortex). We hypothesized a microstructural design of the epicortex that would resist the vertical or shearing stresses. The microstructures of the cortex and epicortex of the rachis and barbs were investigated in several bird species by microbe-assisted selective disassembly and conventional methods via scanning electron microscopy. We report, preeminent of the finds, a novel system of crossed fibres (ranging from ~100-800 nm in diameter), oppositely oriented in alternate layers of the epicortex in the rachis and barbs. It represents the first cross-fibre microstructure, not only for the feather but in keratin per se. The cortex of the barbs is comprised of syncitial barbule cells, definitive structural units shown in the rachidial cortex in a related study. The structural connection between the cortex of the rachis and barbs appears uninterrupted. A new model on feather microstructure incorporating the findings here and in the related study is presented. The helical fibre system found in the integument of a diverse range of invertebrates and vertebrates has been implicated in profound functional strategies, perhaps none more so potentially than in the aerofoil microstructure of the feather here, which is central to one of the marvels of nature, bird flight.
EDİNSEL DİJİTAL FİBROKERATOM: OLGU SUNUMU İyida, Ayşegül Yalçınkaya; Şimşek, Gülçin; TEKİN, Fatih ...
Balıkesir Sağlık Bilimleri Dergisi,
08/2018, Letnik:
7, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Edinsel dijital fibrokeratom (EDF), genellikle parmaklar üzerinde asemptomatik bir nodül olarak saptanan, benign, nadir görülen fibröz bir tümördür. Travma predispozan bir faktör olarak suçlansa da ...etiyolojisi bilinmemektedir. Sıklıkla hiperkeratotik bir yüzeye sahip, deri renginde, yuvarlak ya da parmak benzeri uzantılı, küçük, iyi sınırlı tek lezyon olarak izlenilir. “Hendek” olarak isimlendirilen deri renginden hafifçe koyu bir yakalıkla çevrilidir. Edinsel dijital fibrokeratom genellikle orta yaşlı erişkinlerde görülmektedir. Histopatolojik incelemede epidermisde belirgin hiperkeratoz, akantoz ve dermisde dilate kapillerler ile kalın kollajen demetler izlenmektedir. Kollajen demetleri lezyonun vertikal aksı boyunca sıralanmaktadır. Edinsel dijital fibrokeratomun en etkili tedavisi cerrahi eksizyondur. Burada nadir görülmesi ve dermatolojide parmaklar üzerinde sık görülen diğer hastalıklarla karışabilmesi nedeniyle bir EDF vakası sunuldu.
The epidermis is continuously exposed to environmental hazard and undergoes continuous cell renewal. The maintenance of the epidermal balance between proliferation and differentiation is essential ...for the homeostasis of the skin. Proliferation and terminal differentiation are compartmentalized in basal and suprabasal layers, respectively. These compartments can be identified by different patterns of protein expression that can be used as differentiation markers. For instance, components of the intermediate filament cytoskeleton keratins K5 and K14 are confined to the proliferative basal layer, while keratins K1 and K10, keratins K6 and K16, or precursors of the cornified envelope such as involucrin are expressed by suprabasal terminally differentiating cells. The analysis of the expression of these markers allows studying the imbalance typical of disease. Although these markers have been traditionally analyzed on skin microsections, on attached cells by immunostaining or by western blotting, it is possible and advantageous to quantify them by flow cytometry. We have extensively applied this technology onto human and mouse keratinocytes. Here we describe detailed flow cytometry methods to determine the differentiation status of keratinocyte populations.
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•The wound healing effect of feather keratin was investigated via a rat model.•The biocompatibility tests of feather keratin hydrogel have also been performed.•Compared to human hair ...keratin, feather keratin display similar wound healing effect.
Keratins are highly attractive for wound healing due to their inherent bioactivity, biocompatibility and physical properties. However, nearly all wound healing studies have focused on human hair keratins, and the wound-repair effects and in vivo biocompatibilities of feather keratins are not clear. Feather keratins are derived from chicken feathers, which are considered to be the major waste in the poultry industry, and the quality of feather keratin is easier to control than that of human hair keratin due to human hair perming and colouring-dyeing. Thus, we extracted keratins from chicken feathers, and a feather keratin hydrogel was then prepared and used to test the in vivo wound-healing properties and biocompatibility. The results indicated that feather keratins displayed wound-healing and biodegradation properties similar to those of human hair keratins and were also highly compatible with those of the tissue and devoid of immunogenicity and systematic toxicity. Collectively, these results suggested that feather keratin hydrogel could be used for biomedical applications, particularly effective wound healing.
Pure keratin membrane and fibers from chicken feather Ma, Bomou; Qiao, Xue; Hou, Xiuliang ...
International journal of biological macromolecules,
August 2016, 2016-Aug, 2016-08-00, 20160801, Letnik:
89
Journal Article
Recenzirano
Odprti dostop
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•Keratin was extracted from the chicken feather using l-cysteine as the reductant.•Pure keratin membranes and fibers were fabricated from keratin/buffer solution.•Strength of the ...keratin membrane research up to 3.5MPa with elongation of 127%.
In this research, keratin was extracted from the disposable chicken feather using l-cysteine as reducing agent. Then, it was re-dissolved in the sodium carbonate-sodium bicarbonate buffer, and the pure keratin membrane and fiber were fabricated by doctor-blade casting process and wet spinning method, respectively. Scanning electron microscopy (SEM), fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD) and thermogravimetric analysis (TGA) were used to characterize the chemical and physical properties of resulting powder, membrane and fiber. Compared with the raw chicken feather, the regenerated keratin materials retain its chemical structure and thermal stability, their relative crystallinity is a little different depend on the shaping method, which leads to the difference in moisture regain. The mechanical results show that tensile strength of the keratin membrane researches 3.5MPa, have potential application in biomedical fields. However, the keratin fiber presents low tenacity, i.e. 0.5cN/dtex, this problem should be solved in order to apply the new fiber in textile and material science.
Keratins make up the largest subgroup of intermediate filament proteins and represent the most abundant proteins in epithelial cells. They exist as highly dynamic networks of cytoplasmic 10–12 nm ...filaments that are obligate heteropolymers involving type I and type II keratins. The primary function of keratins is to protect epithelial cells from mechanical and nonmechanical stresses that result in cell death. Other emerging functions include roles in cell signaling, the stress response and apoptosis, as well as unique roles that are keratin specific and tissue specific. The role of keratins in a number of human skin, hair, ocular, oral and liver diseases is now established and meshes well with the evidence gathered from transgenic mouse models. The phenotypes associated with defects in keratin proteins are subject to significant modulation by functional redundancy within the family and modifier genes as well. Keratin filaments undergo complex regulation involving post-translational modifications and interactions with self and with various classes of associated proteins.
This review focuses on the unique family of keratin proteins, whose expression spans ‘hard’ tissues such as hair and ‘soft’ organs such as liver. Exciting recent developments include their involvement in several human diseases, their role in cell signaling and protection from various forms of stress, and the biochemical underpinnings of these functions.
Las células de la pulpa dental humana (hDPCs) han emergido como una alternativa prometedora para la regeneración de tejidos dentales. El factor de crecimiento insulínico tipo 1 (IGF-1) juega un rol ...crucial en la proliferación y diferenciación osteogénica de las hDPCs en condiciones in vitro. No obstante, el impacto del IGF-1 sobre la proliferación y diferenciación odontogénica de las hDPCs en un contexto in vivo aún no ha sido completamente elucidado. En el presente estudio, se extrajeron hDPCs de premolares y terceros molares sanos mediante el uso de colagenasa tipo I y dispasa. La tinción inmunocitoquímica de las hDPCs reveló una reactividad positiva para vimentina y negativa para citoqueratina. El tratamiento con IGF-1 en concentraciones de 50, 75 y 100 ng/mL incrementó de manera significativa y dependiente de la dosis la capacidad proliferativa de las hDPCs. En experimentos in vivo, las hDPCs fueron implantadas en una matriz dérmica acelular y posteriormente trasplantadas de manera subcutánea en ratones desnudos. Tras 2 y 4 semanas de trasplante, la coloración con hematoxilina y eosina evidenció un aumento en la cantidad de células y matriz extracelular en los implantes tratados con IGF-1, mientras que la coloración con Rojo de Alizarina indicó una mayor formación de tejido mineralizado en comparación con el grupo control. El análisis mediante microscopía electrónica de transmisión (TEM) de las hDPCs mostró una abundante presencia de mitocondrias, retículo endoplásmico rugoso y complejos de Golgi. En conclusión, nuestros hallazgos sugieren que el IGF-1 favorece la proliferación de las hDPCs in vitro así como su diferenciación odontogénica in vivo, lo cual señala que la modificación de la señalización del IGF-1 podría ofrecer estrategias potenciales para la regeneración de tejidos dentales.
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