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Recessive dystrophic epidermolysis bullosa (RDEB) is a rare skin fragility disorder characterized by deficient dermo-epidermal adhesion, due to mutations in the gene encoding collagen VII. Patients with RDEB suffer chronic wounds and inflammation that ultimately trigger fibrosis and highly aggressive squamous cell carcinoma development. We previously reported a clinical case of two siblings carrying in homozygosis the same null mutation (c.6527insC) in the COL7A1 gene, but with marked phenotypic differences with respect to the extent of mucocutaneous involvement, skin fragility and fibrosis.
iRHOM2 is a highly conserved, catalytically inactive serine protease. Dominant gain-of-function mutations in RHBDF2, the gene encoding iRHOM2, are causative of Tylosis with oesophageal cancer (TOC). TOC is a syndrome of palmoplantar keratoderma and significantly upregulated risk of oesophageal squamous cell carcinoma development. We previously identified that iRHOM2 interacts with the type I stress-associated Keratin 16 (K16). We have shown TOC patient keratinocytes display elevated K16 levels with a robust downregulation of its associated type II binding partner, Keratin 6 (K6).
SWI/SNF ATP-dependent chromatin remodelling complexes alter nucleosome structure, positioning and chromatin compaction state resulting in target gene activation or repression. The SWI/SNF complexes contain either BRG1 or BRM as the core ATPase together with other common and variable subunits. BRG1 is required for epidermal terminal differentiation in both mice and human; and for hair follicle stem cell activation during mouse hair regeneration and cutaneous wound healing. However, the role of SWI/SNF complexes in human skin wound healing remains unknown.
Previously we showed an inhibitory effect of tropisetron on transforming growth factor (TGF)-beta1-induced collagen synthesis in human dermal fibroblasts (HDFs) which was alpha7 nicotinic acetylcholine receptors (alpha7nAchR) dependent. In vivo data disclose that tropisetron not only reduced but also prevented experimentally-induced skin fibrosis in the bleomycin (BLM) mouse model of scleroderma. To elucidate the role of the alpha7nAchR in fibrosis, we tested PHA-543613, a full agonist of the alpha7nAchR in the BLM mouse model of scleroderma.
A variety of mediators such as cytokines and chemokines properly regulate the process of skin wound repair. Previous study indicated that cytoplasmic DNA-sensor cyclic GMP-AMP synthase (cGAS) activates the stimulator of interferon genes (STING) through production of cyclic GMP-AMP (cGAMP) and is followed by inducing inflammatory cytokines, including type I interferon (IFN). In the present study, we evaluated whether activation of the STING pathway by cGAMP affects the process of skin wound repair.
Skin and wound microbiome have been identified as key modulators of health and disease. Although the general composition of this microbiome follows large trends there are large inter-individual variation. Wound healing is a complex multistep process that involves an inflammatory phase that conditions many of the subsequent stages of healing. Skin barrier rupture results in exposure to bacterial compounds suggesting a key role of the wound microbiome in the healing process. We here aimed to systematically study the skin bacterial composition in normal and wounded animals in 32 different strains of mice from the collaborative cross.
FACIT collagen XII decorates large collagen fibrils within stiff connective tissues. While its mutation or loss causes disorders of connective tissues in humans, its overabundance was described in fibrotic lesions of scleroderma patients and corneal scarring, indicating a vital role of collagen XII in ECM homeostasis. We postulate that collagen XII has the potential to influence tissue properties by linking scaffolding molecules, transmitting signals to cells or by modulating availability of growth factors.
Systemic sclerosis (SSc) is a multisystem autoimmune disease characterized by vasculopathy and extensive fibrosis of the skin and various internal organs. Our previous studies have demonstrated that the deficiency of transcription factor Fli1, which is a predisposing factor of SSc, induces SSc-like phenotypes in dermal fibroblasts, endothelial cells, macrophages and epithelial cells. More importantly, endothelial cell- and epithelial cell-specific Fli1 knockout mice recapitulate vasculopathy and organ fibrosis of SSc, respectively, suggesting that mice with conditional deletion of Fli1 serve as a powerful tool to investigate the pathological process of SSc.
Endothelial cells that line the vascular endothelium undergo a variety of cellular transitions, with one such transition known as endothelial to mesenchymal transition (EndMT). We identified transcription factor Sox9 to be highly expressed in a progenitor population in the endothelium. We here aimed to investigate the potential molecular regulation of EndMT by the transcription factor Sox9 as well as its interaction with Notch signaling. A vascular-specific Sox9 knock-out (Sox9fl/flCdh5CreERt2Rosa-YFP (Sox9eKO)) and a vascular specific rbpj knock-out mouse model were used to assess EndMT.
Aging of fibroblasts impairs skin condition and elasticity, leading to dermal disorders. However, the mechanism of fibroblast aging in real skin is largely unknown, because there are few methods to observe the actual status of fibroblasts in skin. Here we established novel technology to analyze the ultrafine structure of whole skin three-dimensionally (3D), using a new serial-block-face scanning electron microscopy (SBF-SEM) method after electron-conductive pretreatment, which made it possible to observe whole skin.
The regenerative nature of hair follicle (HF) stem cells (SCs) facilitates HF cycling and support skin regeneration. A reduction in HF SC number is a key factor in skin and HF aging and in the development of hair disorders, i.e. androgenetic alopecia and lichen planopilaris. Fruit SC-derived extracts reportedly have positive effects on the regenerative capacity of primary human epidermal SCs. Treatment with apple or grape SC extract increased the colony forming efficacy of primary human epidermal SCs, even under UV stimulation, and restored the organogenic potential of late passage primary human epidermal SCs to generate 3D epidermis in vitro.
During skin aging the dermal thickness decrease dramatically, that lead to a visible reduction in the elasticity of the skin. Different cosmetic products used to increase dermal thickness by rising water and glycosaminoglycan content or stimulation fibroblast function with special nutrients. In our study, we offer to use inhibitors of the enzyme that block degradation of the extracellular matrix and can rise dermal thickness. Enzyme inhibitors Etamsylate have anti hyaluronidase action was used in our study.
Spheroids as microtissues are a powerful alternative to standard 2D cell culture for in vitro studies. 3D scaffold-free spheroids are formed within a few days from a cell suspension using hanging drop technology. The advantages of spheroids exclusively composed of fibroblasts rely on the physiological production of the extracellular matrix thanks to the aggregative capability of fibroblasts to self-assemble in a round tridimensional structure. This microdermis presents a complex tissue organization that closely mimics the architecture and composition of the human dermis in vivo.
Acne is a chronic inflammatory disease of the pilosebaceous follicle. It involves several phases beginning with hyperproduction of sebum, followed by colonization by Cutibacterium acnes, comedogenesis, and subsequent inflammation. Hyperseborrhea is a critical step of acne development. Sebum is composed by the lipids synthesized by sebocytes and the cellular components of these cells released through a holocrine secretion. Our objective was to evaluate the effect of the newly patented anti-acne Silybum marianum fruit extract on the production and regulation of sebum components using two ultimate in vitro models.
The increased incidence of heat stroke is caused by reduced sweating as a result of failures in tissue homeostasis that occur with aging. Specifically, tissue homeostasis is disrupted by the exhaustion of stem cells. We previously revealed that myoepithelial cells are the stem cells of sweat glands, thereby heat stroke can be avoided by preventing myoepithelial cell loss. Although myoepithelial cells serve as a useful tool for revealing their depletion, only a single strain of sweat gland cells, NCL-SG3, can differentiate into mature cells in adherent culture conditions.
In this study we investigated the effect of four botanical extracts derived from jasmine, Longoza, peony and lily on human skin cells. Firstly we used a proteomic approach in order to highlight main biological pathways enhanced by our extracts. Then we evaluated the ability of a combination of these four extracts to protect stem cells. First of all we proceed to protein identification and relative quantification using LC-MS/MS method on skin cells treated or not with each of our botanical extracts.
The exposure of hair and scalp to air pollutants has been associated with a pro-oxidant effect, increased AhR (Aryl hydrocarbon Receptor) signaling and inflammation status, reduced microvasculature in the dermal papilla, decreased melanin synthesis in the hair bulb, as well as increased sebum secretion and scalp sensitivity. in vitro and ex vivo models were used to investigate the effect of pollution, including cultures of keratinocytes from scalp skin, 3D spheres of human dermal papilla cells or ex vivo scalp biopsies, that were exposed to PM2.5 or cigarette smoke.
Xenografting of human skin to the immunodeficient mice is one of the most invaluable approaches for the in vivo investigation of human hair follicle morphogenesis. In our study we have established a model of human skin transplantation to nude mice enabling the investigation of in vivo morphogenesis of human hair follicles. Strips of full-thickness human adult scalp skin (0.5x2 cm) taken from hair-bearing areas of normal individuals were grafted onto the back of nude mice using mouse skin flap technique to prevent graft drying.
Hair transplantation is used routinely for the management of androgenetic alopecia, the most common cause of hair loss. However, patients must have enough donor hair follicles (HFs) for transplant surgery. Alternative technologies that could potentially generate HFs in vitro would be beneficial. Efforts to recapitulate HF morphogenesis, using mouse embryonic cells or primary human adult epidermal or outer root sheath (ORS) keratinocytes, in combination with human primary dermal papilla fibroblasts (DPs), have been largely unsuccessful.
Delivery of active molecules to the hair follicle for the purpose of hair growth promotion or inhibition is complicated by the concomitant undesired delivery of the molecules to interfollicular epidermis. We describe a new formulation designed to specifically penetrate the vacant hair follicle during epilation while avoiding epidermal cells. Using a combination of short chain esters and ethanol we were able to deliver an aqueous solution of hydrogen peroxide to human hair follicles from normal skin biopsies by means of epilation carried out with a standard epilator, followed by histology, H&E and cleaved caspase 3 staining.