Increased Cholesterol Sulfate and Cholesterol Sulfotransferase Activity in Relation to the Multi-step Process of Differentiation in Human Epidermal Keratinocytes

Regulation of type I (epidermal) transglutaminase mRNA levels during squamous differentiation: down regulation by retinoids.

“…However, this would not preclude the presence in squamous-differentiated cells (and hence in our cDNA library) of the mRNA for the type II transglutaminase. To determine which of these two mRNAs is represented by the pTG-7 family of cDNA clones, we undertook an analysis of mRNA levels in NHEK cells, which can express moderate levels of both type I and II transglutaminase proteins (16,36 Fig. 1) was sequenced (Fig.…”

“…Retinoic acid suppressed this increase in the level of type I transglutaminase mRNA. P S C R (16,36). Most of the evidence has tended to suggest that type I and II transglutaminases do constitute distinct proteins, encoded by different transcriptional units, as evidenced by differences in apparent molecular mass (92 and 85 kilodaltons), subcellular distribution (particulate or soluble), chromatographic properties, and immunoreactivity (22,29,36).…”

“…For some experiments, additional components were added to the medium as indicated in the text. Normal human epidermal keratinocytes (NHEK cells) were obtained from Clonetics Corp., Palo Alto, Calif., and grown in KGM medium as previously described (16).…”

Multistep Process of Squamous Differentiation in Tracheobronchial Epithelial Cells In Vitro: Analogy with Epidermal Differentiation

“…Recently, the accumulation of cholesterol sulfate has been shown to be associated with squamous cell differentiation in tracheobronchial and epidermal epithelial cells in culture (63)(64)(65). The increase in cholesterol sulfate has been related to an increase in the enzyme cholesterol sulfotransferase (68).…”

“…Retinoids do not block the commitment to terminal cell division in tracheobronchial or epidermal cells induced by confluence, withdrawal of EGF and insulin or addition of TGF-P or PMA (43,64,73); however, retinoids do block the expression of the differentiated phenotype. Retinoids inhibit the induction of transglutaminase type I (54,(99)(100)(101)(102) and cholesterol sulfotransferase activities, inhibit the accumulation of cholesterol sulfate (63)(64)(65)(66), and inhibit cornification in several in vitro tracheobronchial and epidermal cell systems (39,43,(103)(104)(105) (115,116). This receptor protein is homologous to the receptors for steroid honnones, thyroid hormones, and vitamin D3 and appears to be a retinoic acid-inducible, trans-acting enhancer factor.…”