Epithelial keratins

Squamous cell carcinomas of different sites of origin are generally characterized by a predominance of stratified-epithelial/keratinocyte-type keratins but may coexpress certain simple-epithelial keratins (for details, see Moll 1998). Most of these... 

Owens DW, Lane EB (2003) The quest for the function of simple epithelial keratins. Bioessays 25(8) 748 758... 

The role of the IF, and particularly the keratin filament system, in resisting the forces of mechanical stress has been well established. However, IFs also play a role in countering metabolic stress. Perhaps the best example is the cytoprotective role played by the simple epithelial keratins, K8/18. However, vimentin, desmin, peripherin, GFAP, the lens proteins phakinin, and filensin and other keratins have also been shown to associate with members of the small heat shock protein (HSP) family, including HSP27 and aB-crystallin (reviewed in Coulombe and Wong, 2004 Marceau et al., 2001 Nicholl and Quinlan, 1994). 

Liao,J., and Omary, M. B. (1996). 14-3-3 proteins associate with phosphorylated simple epithelial keratins during cell cycle progression and act as a solubility cofactor. / Cell. Biol. 133, 345-357. 

The soft epithelial keratin intermediate filaments comprise approximately 20 different keratin polypeptides. " The polypeptides, numbered 1 through 20, comprise type II (basic) keratins and type I (acidic) keratins (Table 8.2). This family of intermediate filaments is crucial in diagnostic IHC for the identification of carcinomatous differentiation and for identification of specific carcinoma subtypes. 

Simple epithelial keratins are the first keratins to appear in embryonic development because they are expressed in virtually all simple (nonstratified), ductal, and pseudo-stratified epithelial tissuesd° >ii° Because these keratins... 

Nash SV, Said JW. Gastroenteropancreatic neuroendocrine tumors. A histochemical and immunohistochemical study of epithelial (keratin proteins, carcinoembryonic antigen) and neuroendocrine (neuron-specific enolase, bombesin and chromo-granin) markers in foregut, midgut, and hindgut tumors. Am J Clin Pathol. 1986 86 415-422. 

Tables II and III are summary compilations of the relative biologic activities of chlorinated dibenzo-p-dioxins and furans, respectively, as measured by in vitro tests such as enzyme induction, epithelial keratinization or the "flat cell" effect in XB/3T3 cell cultures.

To note, intermediate filaments are cytoskeletal structures that are formed by different members of a family of related, highly conserved proteins (Godsel et al. 2008). Most types of intermediate filaments are located in the cytoplasm. The nuclearly localized intermediate filaments are called lamins. Categorization of intermediate filaments into six groups has been done on the basis of similarities in amino acid sequence and protein structure. Types I and II intermediate filaments are acidic and basic keratins, namely epithelial keratins and trichocytic keratins (e.g., in hair and horns). Type III intermediate filaments are, e.g., vimentin (widely expressed in fibroblasts), Type IV intermediate filaments are, e.g., neurofilaments, type V intermediate filaments are nuclear lamins, type VI intermediate filaments are nestin. A well-known disease resulting from... 

Although Wolfs experiments have opened a new avenue, a molecular explanation of the mechanism of epithelial keratinization observed in vitamin A deficiency is still not available. Russian investigators have proposed that the effect of the vitamin on keratiniza-tion is secondary to its effect on oxidative processes. They claim that the oxidation of cysteine to cystine is a rate-limiting step in keratin formation, that copper catalyzes this oxidation, and that carotinoids inhibit the oxidative role of copper, thereby preventing the oxidation of SH groups into a disulfide bond. 

Smith TA, Parry DAD (2007) Sequence analyses of Type I and Type II chains in human hair and epithelial keratin intermediate filaments promiscuous obligate heterodimers. Type II template for molecule formation and a rationale for heterodimer formation. J Struct Biol... 

Hydroxyapatite crystals are usually confined to areas where there is a need for high mechanical strength, rigidity or hardness as in bone, dentine and enamel. They do not normally occur at all in soft tissues , the only other site of occasional local occurrence being within such epithelial keratins as hard claws and beaks. 

It is a lipophilic compound which removes intercellular lipids that are covalently linked to the cornified envelope surrounding epithelial cells [3]. It also enhances penetration of other agents. Resorcinol (m-dihydroxy benzene) is structurally and chemically similar to phenol. It disrupts the weak hydrogen bonds of keratin [4]. Lactic acid is an alpha hydroxy acid which causes corneocyte detachment and subsequent desquamation of the stratum corneum [5]. 

Keratinization, the sloughing of epithelial cells in the hair follicle, is also a natural process. In acne, however, hyperkem-tinization occurs and causes increased adhesiveness of the sloughed cells. Accumulation of these cells clogs the hair follicle, blocks the flow of sebum, and forms an acne lesion called an open comedo or blackhead. ... 

May be applied to both keratinized epithelial and mucosal surfaces. 

Cholesteatoma A mass of keratinized epithelial cells and cholesterol resembling a tumor that forms in the middle ear or mastoid region. 

Types I and II are the keratins that are found in various combinations in epithelial cells throughout the body. Keratin IFs must include representative subunits of both type I and type II IF subunits with each tissue having a characteristic combination. In contrast, type III IF subunits typically form homopolymers. They include IFs that are characteristic of less differentiated cells like glial or neuronal precursors, as well as those seen in more specialized cell types like smooth muscle cells and mature astrocytes. These three types of IF not only share sequence homology within their rod domains but their genes... 

Keratins are alpha-type fibrous polypeptides with a diameter of 7 11 nm. They are important components of the cytoskeleton in almost all epithelial cells as well as in some nonepithelial cell types. Keratins are generally held to be the most ubiquitous markers of epithelial differentiation. So far, 20 distinct types numbered by Moll et al. (1982a, 1990, 1992) have been revealed. Keratins were earlier thought to be separable into hard and soft, or cytokeratins and other keratins, but these designations are now understood to be incorrect. In 2006, a new nomenclature (Schweizer et al. 2006) was adopted for describing keratins which takes this into account (Table 13.1). 

Chu PG, Weiss LM (2002a) Expression of cytokeratin 5/6 in epithelial neoplasms an immuno histochemical study of 509 cases. Mod Pathol 15(1) 6 10 Chu PG, Weiss LM (2002b) Keratin expression in human tissues and neoplasms. Histopathology 40(5) 403 439... 

Moll R, Franke WW, Vole Platzer B, Krepler R (1982b) Different keratin polypeptides in epider mis and other epithelia of human skin a specific cytokeratin of molecular weight 46,000 in epithelia of the pilosebaceous tract and basal cell epitheliomas. J Cell Biol 95(1) 285 295 Moll R, Krepler R, Franke WW (1983) Complex cytokeratin polypeptide patterns observed in certain human carcinomas. Differentiation 23(3) 256 269 Moll R, Dhouailly D, Sun TT (1989) Expression of keratin 5 as a distinctive feature of epithelial and biphasic mesotheliomas. An immunohistochemical study using monoclonal antibody AE14. Virchows Arch B Cell Pathol Incl Mol Pathol 58(2) 129 145 Moll R, Schiller DL, Franke WW (1990) Identification of protein IT of the intestinal cytoskeleton as a novel type I cytokeratin with unusual properties and expression patterns. J Cell Biol 111(2) 567 580... 

T. Kai, T. Isami, Y. Kurosaki, T. Nakayama, and T. Kimura. Keratinized epithelial transport of beta-blocking agents. II. Evaluation of barrier property of stratum corneum by using model lipid systems. Biol. Pharm. Bull. 16 284—287 (1993). 

The use of buccal cell cultures for assessing the permeability of the buccal mucosa has attracted recent attention (see Chap. 7 for a more extensive summary). In order to culture buccal epithelial cells, the cells must be harvested from an appropriate source and cultured under specific conditions using an appropriate growth medium, temperature, and humidity [46], Cell cultures have been successfully grown from hamster cheek pouch. These cultured cells, however, did not differentiate to form a complete keratinized surface as seen in the normal hamster cheek pouch, and they consequently displayed a greater permeability to compounds when compared with keratinized hamster cheek pouch mucosa [134], Therefore, the cultured hamster cheek cells more closely mimicked the human buccal mucosa due to their lack of keratinization, and so this may be an appropriate model for predicting permeability through the human buccal mucosa. 

Tsutsumi K, Obata Y, Takayama K, Isowa K, Nagai T (1999) Permeation of several drugs through keratinized epithelial-free membrane of hamster cheek pouch. IntJ Pharm 177 7-14... 

Another 3-D cornea model, comprising rabbit primary cultures of epithelial and stromal cells as well as mouse immortalized endothelial cells, was described in 1994 by Zieske and coworkers [70], They showed the influence of endothelial cells on the formation of a tightly packed, multilayered epithelium as well as the expression of laminin, type VII collagen, a6 integrin, keratin K3, and a-enolase. Furthermore, their findings suggested that the formation of an in vivo-like epithelium requires the cultivation of the 3-D corneal construct under AIC conditions. By contrast, LCC methods of cultivating corneal equivalents in the absence of endothelial cells failed to promote the expression of differentiation markers and basement membrane components. 

In another approach, Parnigotto and coworkers reconstructed corneal structures in vitro by using corneal stroma containing keratocytes to which corneal epithelial cells from bovine primary cultures were overlaid [73], However, this particular corneal model did not contain an endothelial layer. This model was histochemically characterized and the toxicity of different surfactants was tested using MTT methods. This stroma-epithelium model has been reported to show a cornea-like morphology, where a multilayered epithelial barrier composed of basal cells (of a cuboidal shape) and superficial cells (of a flattened shape) is noted. Furthermore, the formation of a basement membrane equivalent and expression of the 64-kDa keratin were reported, indicating the presence of differentiated epithelial cells. The toxicity data for various surfactants obtained with this model correlate well with those seen by the Draize test [73], However, this corneal equivalent was not further validated or used as a model for permeation studies. 

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