Involucrin

Abstract: The mucosal lining of the oral cavity and esophagus functions to protect the underlying tissue from mechanical damage and from the entry of microorganisms and toxic materials that may be present in the oropharynx. In different regions, the mucosa shows adaptation to differing mechanical demands: Masticatory mucosa consists of a stratified squamous keratinized epithelium tightly attached to the underlying tissues by a collagenous connective tissue, whereas lining mucosa comprises a nonkeratinized epithelium supported by a more elastic and flexible connective tissue. The epithelium is constantly replaced by cell division in the deeper layers, and turnover is faster in the lining than in the masticatory regions. Chemotherapeutic agents and radiation limit proliferation of the epithelium so that it becomes thin or ulcerated; this will first occur in the lining regions. The principal patterns of epithelial differentiation are represented by keratinization and nonkeratinization. As keratinocytes enter into differentiation, they become larger and begin to flatten and to accumulate cytokeratin filaments. In addition to the keratins, the differentiating keratinocytes synthesize and retain a number of specific proteins, including profilaggrin, involucrin, and other precursors of the thickening of the cell envelope in the most superficial layers. The concept of epithelial homeostasis implies that cell production in the deeper layers will be balanced by loss of cells from the surface. There is a rapid clearance of surface cells, which acts as a protective mechanism by limiting colonization and invasion of microorganisms adherent to the mucosal surface.

Abstract: A specialized tissue type, the keratinizing epithelium, protects terrestrial mammals from water loss and noxious physical, chemical and mechanical insults. This barrier between the body and the environment is constantly maintained by reproduction of inner living epidermal keratinocytes which undergo a process of terminal differentiation and then migrate to the surface as interlocking layers of dead stratum corneum cells. These cells provide the bulwark of mechanical and chemical protection, and together with their intercellular lipid surroundings, confer water-impermeability. Much of this barrier function is provided by the cornified cell envelope (CE), an extremely tough protein/lipid polymer structure formed just below the cytoplasmic membrane and subsequently resides on the exterior of the dead cornified cells. It consists of two parts: a protein envelope and a lipid envelope. The protein envelope is thought to contribute to the biomechanical properties of the CE as a result of cross-linking of specialized CE structural proteins by both disulfide bonds and N(epsilon)-(gamma-glutamyl)lysine isopeptide bonds formed by transglutaminases. Some of the structural proteins involved include involucrin, loricrin, small proline rich proteins, keratin intermediate filaments, elafin, cystatin A, and desmosomal proteins. The lipid envelope is located on the exterior of and covalently attached by ester bonds to the protein envelope and consists of a monomolecular layer of omega-hydroxyceramides. These not only serve of provide a Teflon-like coating to the cell, but also interdigitate with the intercellular lipid lamellae perhaps in a Velcro-like fashion. In fact the CE is a common feature of all stratified squamous epithelia, although its precise composition, structure and barrier function requirements vary widely between epithelia. Recent work has shown that a number of diseases which display defective epidermal barrier function, generically known as ichthyoses, are the result of genetic defects of the synthesis of either CE proteins, the transglutaminase 1 cross-linking enzyme, or defective metabolism of skin lipids.