A noncanonical-GPRC5A signaling regulates keratinocyte adhesion and migration by nuclear translocation.

G-Protein Coupled Receptor, Class C, Group 5, Member A (GPRC5A) has been extensively studied in lung and various epithelial cancers. Nevertheless, its role in the skin remains to be elucidated. In this study, we sought to investigate the function of this receptor in skin biology.

The regenerative potential of autologous stem and somatic cells in vitiligo.

Vitiligo is a human pigmentary disorder characterized by autoimmune destruction of mature melanocytes in the skin. In addition to studies on the inflammatory component of the disease, current treatments tend to involve stimulation of local melanocyte stem cells or transplantation of functional melanocytes from uninjured areas, however, in some cases of extensive depigmentation, only a few healthy cells can be obtained. This review discusses examples in the literature of the use of different sources of autologous stem and somatic cells in order to obtain melanocyte progenitors or mature melanocytes, and compares the strategy of stem cell differentiation with that of somatic cell reprogramming.

Dill Extract Preserves Dermal Elastic Fiber Network and Functionality: Implication of Elafin.

Introduction: Elastic skin fibers lose their mechanical properties during aging due to enzymatic degradation, lack of maturation, or posttranslational modifications. Dill extract has been observed to increase elastin protein expression and maturation in a 3D skin model, to improve mechanical properties of the skin, to increase elastin protein expression in vascular smooth muscle cells, to preserve aortic elastic lamella, and to prevent glycation.

Objective: The aim of the study was to highlight dill actions on elastin fibers during aging thanks to elastase digestion model and the underlying mechanism.

Characterization of the Zebrafish () Mutant: A New Model of Elastinopathy Leading to Heart Valve Defects.

Elastic fibers are extracellular macromolecules that provide resilience and elastic recoil to elastic tissues and organs in vertebrates. They are composed of an elastin core surrounded by a mantle of fibrillin-rich microfibrils and are essentially produced during a relatively short period around birth in mammals. Thus, elastic fibers have to resist many physical, chemical, and enzymatic constraints occurring throughout their lives, and their high stability can be attributed to the elastin protein.

Physiological Impact of a Synthetic Elastic Protein in Arterial Diseases Related to Alterations of Elastic Fibers: Effect on the Aorta of Elastin-Haploinsufficient Male and Female Mice.

Elastic fibers, made of elastin (90%) and fibrillin-rich microfibrils (10%), are the key extracellular components, which endow the arteries with elasticity. The alteration of elastic fibers leads to cardiovascular dysfunctions, as observed in elastin haploinsufficiency in mice () or humans (supravalvular aortic stenosis or Williams-Beuren syndrome). In and mice, we evaluated (arteriography, histology, qPCR, Western blots and cell cultures) the beneficial impact of treatment with a synthetic elastic protein (SEP), mimicking several domains of tropoelastin, the precursor of elastin, including hydrophobic elasticity-related domains and binding sites for elastin receptors.

Zebrafish as a Model to Study Vascular Elastic Fibers and Associated Pathologies.

Many extensible tissues such as skin, lungs, and blood vessels require elasticity to function properly. The recoil of elastic energy stored during a stretching phase is provided by elastic fibers, which are mostly composed of elastin and fibrillin-rich microfibrils. In arteries, the lack of elastic fibers leads to a weakening of the vessel wall with an increased risk to develop cardiovascular defects such as stenosis, aneurysms, and dissections.

Silencing Recapitulates Hypoxic Conditions and Induces Elastic Fiber Impairment in Human Dermal Fibroblasts.

Most chronic wounds are characterized by varying degrees of hypoxia and low partial pressures of O that may favor the development of the wound and/or delay healing. However, most studies regarding extracellular matrix remodeling in wound healing are conducted under normoxic conditions. Here, we investigated the consequences of hypoxia on elastic network formation, both in a mouse model of pressure-induced hypoxic ulcer and in human primary fibroblasts cultured under hypoxic conditions.

Design and characterization of an in vivo injectable hydrogel with effervescently generated porosity for regenerative medicine applications.

Injectable hydrogels that polymerize directly in vivo hold significant promises in clinical settings to support the repair of damaged or failing tissues. Existing systems that allow cellular and tissue ingrowth after injection are limited because of deficient porosity and lack of oxygen and nutrient diffusion inside the hydrogels. Here is reported for the first time an in vivo injectable hydrogel in which the porosity does not pre-exist but is formed concomitantly with its in situ injection by a controlled effervescent reaction.

Versatile lysine dendrigrafts and polyethylene glycol hydrogels with inherent biological properties: in vitro cell behavior modulation and in vivo biocompatibility.

Poly(ethylene glycol) (PEG) hydrogels have been extensively used as scaffolds for tissue engineering applications, owing to their biocompatibility, chemical versatility, and tunable mechanical properties. However, their bio-inert properties require them to be associated with additional functional moieties to interact with cells. To circumvent this need, we propose here to reticulate PEG molecules with poly(L-lysine) dendrigrafts (DGL) to provide intrinsic cell functionalities to PEG-based hydrogels.

Combination of biocompatible hydrogel precursors to apatitic calcium phosphate cements (CPCs): Influence of the in situ hydrogel reticulation on the CPC properties.

In the field of bone regenerative medicine, injectable calcium phosphate cements (CPCs) are used for decades in clinics, as bone void fillers. Most often preformed polymers (e.g.

Substrate softness promotes terminal differentiation of human keratinocytes without altering their ability to proliferate back into a rigid environment.

Substrate stiffness is a key regulator of cell behavior. To investigate how mechanical properties of cell microenvironment affect the human keratinocyte, primary cells were seeded on polyacrylamide hydrogels of different compliances (soft: 4 kPa, medium: 14 kPa, rigid: 45 kPa) in comparison with glass coverslip (> GPa). Keratinocyte spreading and proliferation were strongly decreased on the softest hydrogel, while no significant difference was observed between medium, rigid hydrogels and glass coverslip, and cells' viability was comparable in all conditions after 72 h.

In vitro epidermis model mimicking IGF-1-specific age-related decline.

Ageing is a complex multifaceted process affecting skin functionality and structure. Several 3D organotypic skin culture models have reproduced ageing by inducing replicative senescence, glycation or oxidative stress. Yet, very few models have focused on hormonal ageing and especially the insulin-like growth factor 1 (IGF-1) signalling pathway, which has been associated with longevity in animal studies and is necessary for the early stages of skin development.

Methylation of LOXL1 Promoter by DNMT3A in Aged Human Skin Fibroblasts.

Lysyl oxidase-like 1 (LOXL1) is an amino-oxidase involved in maturation of elastic fibers. Its downregulation has been associated with elastic fibers repair loss in aging aorta, lung, ligament, and skin. Several evidences of LOXL1 epigenetic silencing by promoter methylation were reported in cancer and cutis laxa syndrome.

Magnesium Modifies the Structural Features of Enzymatically Mineralized Collagen Gels Affecting the Retraction Capabilities of Human Dermal Fibroblasts Embedded within This 3D System.

Mineralized collagen gels have been developed as models to better understand the mechanisms regulating the calcification process and the behavior of a variety of cell types. The vast majority of data are related to stem cells and to osteoblast-like cells, whereas little information is available for dermal fibroblasts, although these cells have been associated with ectopic calcification and consequently to a number of pathological conditions. Therefore, we developed and characterized an enzymatically mineralized collagen gel in which fibroblasts were encapsulated within the 3D structure.

Endothelium microenvironment sensing leading to nitric oxide mediated vasodilation: a review of nervous and biomechanical signals.

Blood vessels are continuously exposed to various stresses such as mechanical strains and neurosignals. Besides its role as a barrier between blood and other tissues, the endothelium is a highly important cell layer for the regulation of vascular tone. Indeed, depending on the signal perceived by endothelial cells, it can drive a vasoconstrictor or vasodilator signal.

Rheological behaviour of reconstructed skin.

Reconstructed skins have been developed to replace skin when the integrity of tissue has been compromised following severe injury, and to provide alternative methods validating the innocuousness and effectiveness of dermatological and cosmetic products. However the functional properties of tissue substitutes have not been well characterised, mainly since mechanical measurement devices have not been designed to test cell culture materials in vitro. From the mechanical standpoint, reconstructed skin is a heterogeneous multi-layer viscoelastic material.

Insulin-transferrin-selenium as an alternative to foetal serum for epidermal equivalents.

Objective: Organotypic skin models are powerful tools for research in development, ageing and diseases. They have become more and more complex with the use of multiple cell types. This requires a culture medium adapted to optimize the development of such in vitro skin.

Biosynthetic support based on dendritic poly(L-lysine) improves human skin fibroblasts attachment.

Poly(L-lysine) (PLL) dendrigrafts (DGLs) are arborescent biosynthetic polymers of regular and controlled structures. They have specific properties such as biocompatibility and non-immunogenicity, and their surface density of NH2 functions can be easily modified and therefore appears as a powerful tool for the functionalization of hydrophobic polymers used in the context of tissue engineering. In this study, we evaluated several criteria of human skin fibroblasts when cultured with DGL of generations 2, 3 and 4, with linear PLL polymer as reference.

In vivo skin biophysical behaviour and surface topography as a function of ageing.

Normal skin ageing is characterised by an alteration of the underlying connective tissue with measurable consequences on global skin biophysical properties. The cutis laxa syndrome, a rare genetic disorder, is considered as an accelerated ageing process since patients appear prematurely aged due to alterations of dermal elastic fibres. In the present study, we compared the topography and the biomechanical parameters of normal aged skin with an 17 year old cutis laxa patient.

Lysyl oxidase silencing impairs keratinocyte differentiation in a reconstructed-epidermis model.

Lysyl Oxidase (LOX) is an extracellular enzyme involved in the maturation of connective tissues. It also acts in many cell types as a regulator of cell behaviour and phenotype through intracellular signalling pathways. Recently, LOX was shown to be present in human epidermis where its precise functions remain unclear.

Epigenetic silencing of lysyl oxidase-like-1 through DNA hypermethylation in an autosomal recessive cutis laxa case.

We have recently reported a case of cutis laxa caused by a fibulin-5 missense mutation (p.C217R). Skin fibroblasts from this individual showed an abnormal pattern of expression of several genes coding for elastic fiber-related proteins, including lysyl oxidase-like-1 (LOXL1).

Characterization of the mechanical properties of a dermal equivalent compared with human skin in vivo by indentation and static friction tests.

Background/aims: The study of changes in skin structure with age is becoming all the more important with the increase in life. The atrophy that occurs during aging is accompanied by more profound changes, with a loss of organization within the elastic collagen network and alterations in the basal elements. The aim of this study is to present a method to determine the mechanical properties of total human skin in vivo compared with dermal equivalents (DEs) using indentation and static friction tests.

Self-etching increases matrix metalloproteinase expression in the dentin-pulp complex.

In adhesive restorations, one major problem is hybrid layer degradation. At present, this deterioration is explained by the activation of the endogenous matrix metalloproteinases (MMPs) present in dentin due to the acidic property of adhesive systems. We hypothesized that self-etching adhesive should also stimulate the expression of MMPs in odontoblasts.

Ceramide inhibition of MMP-2 expression and human cancer bronchial cell invasiveness involve decreased histone acetylation.

Ceramides have been proposed as potential therapeutic strategy with regard to their ability to induce cell death. We previously demonstrated that C2-ceramide generated apoptosis in bronchocarcinoma BZR cells. We here investigated whether ceramides also target other molecules involved in cell-cell or cell-matrix interactions during cancer progression.