Retinoic acid receptor isoform RAR gamma 1: an antagonist of the transactivation of the RAR beta RARE in epithelial cell lines and normal human keratinocytes.

The diversity of isoforms of retinoic acid (RA) receptors (RARs) and of DNA sequences of retinoic acid-responsive elements (RAREs) suggests the existence of selectivities in the RAR/RARE recognition or in the subsequent gene modulation. Such selectivities might be particularly important for RAREs involved in positive feedback, eg. the RAR beta RARE.

Influence of formulation, receptor fluid, and occlusion, on in vitro drug release from topical dosage forms, using an automated flow-through diffusion cell.

An automated flow-through diffusion cell apparatus was used for comparing the release rates of a naphthoic acid derivative, CD 271, from different topical formulations. The influence of the following parameters on CD 271 release from the formulations was investigated: receptor fluid composition, occlusion, weight of tested formulation, and dosage form type. The amount of tested formulation was shown to have no significant effect on the apparent release constant and lag time for an anionic oil-in-water emulsion and an aqueous gel.

The rhino mouse model: the effects of topically applied all-trans retinoic acid and CD271 on the fine structure of the epidermis and utricle wall of pseudocomedones.

The histological and ultrastructural effects following 3 weeks' topical treatment with two agents (all-trans retinoic acid and a new synthetic retinoid-like substance, CD271) were evaluated on the epidermis and the epithelial wall of the pseudocomedones in rhino mouse skin. The comedolytic effects of these drugs were similar, and consisted of a reduction of the utricular diameter, with normalization of follicular units. Morphological examinations revealed a hyperplastic response with an increase in the number of cell layers of both epidermis and follicular epithelium, and modifications in keratinocyte differentiation.

Physiology of the vellus hair follicle: hair growth and sebum excretion.

The growth of vellus hair and the secretion of sebum from vellus hair follicles were measured on the forehead, cheek, chest, shoulder and back of healthy men and women aged 15-30 years. Hair growth was assessed by computerized image-analysis of photographs and sebum excretion by the use of Sebutape followed by image analysis. The density of vellus hairs and the percentage of growing hairs were higher on the face than on the thorax (439 hairs/cm2 with 49% growing hairs on the forehead compared with 85 hairs/cm2 with 31.

Isolation of a GC-rich cDNA identifying mRNA present in human epidermis and modulated by calcium and retinoic acid in cultured keratinocytes. Homology with murine loricrin mRNA.

Differential screening of a human epidermal cDNA library led to the isolation of cDNA clones homologous to mRNAs specifically expressed in epidermis but weakly or not expressed in the undifferentiated squamous carcinoma cell line TR146. One of these 'differentiation-specific' cDNA clones, A8, hybridized with a 1.7 kb transcript among RNAs isolated from normal human epidermis, but with several transcripts ranging from 1.

Cornified envelopes in congenital disorders of keratinization.

A morphological and biochemical analysis was made of cornified envelopes isolated from patients with different congenital disorders. Nomarski contrast microscopy of the envelopes showed that their morphology was not greatly altered in several types of keratoderma and parapsoriasis, but it was grossly modified in ichthyotic disorders. The various types of ichthyoses, keratoderma palmoplantare, KID syndrome and parapsoriasis showed, after cyanogen-bromide cleavage, peptide patterns similar to those obtained from healthy subjects.

The physiology and biochemistry of retinoic acid.

The ability of the fat soluble Vitamin A to modulate cellular differentiation has been known for over 60 years. Numerous studies have shown that Vitamin A and its 2 major metabolites play a key role in vision (retinal) and cell differentiation (retinoic acid, RA). The control of cellular differentiation may be exercised on a variety of tissues including simple and stratified epithelia, the latter will be the focal point of this article, with emphasis being given to the skin.

Retinoic acid inhibits the production of collagenase by human epidermal keratinocytes.

Lattices made of collagen and fibroblasts can be used as dermal equivalents to grow human keratinocytes in vitro. When these cultures are performed in a medium containing delipidized serum, the lattice is eventually degraded by the growing epithelium. The digestion of the dermal equivalent is due to the secretion of a collagenase by the keratinocytes.

Retinoic acid controls expression of epidermal transglutaminase at the pre-translational level.

Human epidermal keratinocytes were cultured until sub-confluence in low Ca2+ (0.15 mM) serum-free synthetic MCDB 153 medium. Raising the Ca2+ concentration to 1.

Retinoic acid improves epidermal morphogenesis.

Hyper- and hypovitaminosis A both provoke epithelial pathologies in animals and humans. This suggests that a critical level of retinoic acid (RA) is required in vivo for the maintenance of normal architecture and function of these tissues. However, no beneficial, but only adverse effects of RA on epithelia have been so far observed in vitro.

Bioassays for retinoic acid-like substances using cultured human keratinocytes.

Using cultured human keratinocytes, three bioassays for retinoic acid-like substances have been developed. They are based on the ability of these substances (1) to inhibit cross-linked envelope formation, (2) to inhibit the synthesis of the K1 keratin, and (3) to stimulate the synthesis of the K19 keratin. The data, expressed as 50% inhibitory or activating concentrations were used to rank compounds according to their activity.

Outer root sheath cells of human hair follicle are able to regenerate a fully differentiated epidermis in vitro.

During wound healing, interfollicular epidermis can be regenerated from the outer root sheath of hair follicles, showing that the cells of this structure can shift toward an interfollicular epidermal phenotype. Similarly, it has been shown that a multilayered epithelium originating from outer sheath cells can be obtained in vitro by culturing hair follicles. However, in the culture systems developed so far, the phenotypical shift was incomplete since the cells retained some of their original characteristics and did not acquire several key markers of terminally differentiated epidermis.

Differentiation of normal and tumoral human keratinocytes cultured on dermis: reconstruction of either normal or tumoral architecture.

Normal human keratinocytes isolated from skin and squamous carcinoma cells established from a human tumor (TR146 cell line) both exhibit limited morphologic differentiation when they are grown on conventional plastic dishes. However, when they are seeded on human de-epidermized dermis and cultured at the air-liquid interface, they are able to reform an epithelium having the morphology of the tissue of origin (i.e.

Abnormal sequence of expression of differentiation markers in psoriatic epidermis: inversion of two steps in the differentiation program?

This immunohistologic study was undertaken to compare epidermal differentiation in normal and psoriatic skin. Although basal cells retain a normal phenotype in this disease, suprabasal layers exhibit abnormal sets of differentiation markers. The 67-kD keratin and Bd5 antigen, which are found in normal epidermis immediately above the basal layer, appear several layers higher in involved psoriatic epidermis.

An improved assay procedure and a new chemically stable ligand for cytosolic retinoic acid binding protein.

A high through-put method to assay for binding of retinoids to their cytosolic binding protein is described. The protein-bound retinoid is quantified following its complete separation from the free ligand by a single gel filtration chromatography step on Sephadex G-25 columns. The method allows a single person to process up to 100 samples per day.

Plasma membrane transglutaminase and cytosolic transglutaminase form distinct envelope-like structures in transformed human keratinocytes.

Cross-linked envelope formation in the transformed human keratinocyte line SV-K14 requires treatment of the cells with a Ca2+ ionophore. Depending on the culture conditions, different extracellular Ca2+ concentrations are necessary to trigger the process which is catalyzed by the enzyme transglutaminase. Confluent cells grown in the presence of serum express only the cytosoluble form of the enzyme and need 5 mM Ca2+ for optimum protein cross-linking, whereas serum-starved cells which additionally contain the plasma membrane associated form of the enzyme require only 1 mM Ca2+.

Hexadecane-induced skin hyperplasia in the hairless rat: time course of histological and biochemical events related to the synthesis of polyamines and DNA.

Several biochemical parameters including ornithine decarboxylase activity (ODC) and tissue polyamine levels were measured during the hexadecane-induced epidermal hyperplasia of hairless rat skin. Animals received three applications of 200 microliters pure n-hexadecane on day 1. ODC activity and polyamine levels (putrescine, spermidine and spermine) in the epidermis were significantly increased and reached maximum elevations at 12 h after the start of n-hexadecane treatment with DNA synthesis peaking at 24 h.