In epithelial differentiation

Four major MT isoforms, MT-1, MT-2, MT-3, and MT-4, have been identified in mammals. The most widely expressed isoforms in mammals, MT-1 and MT-2, are rapidly induced in the liver by a wide range of metals, drugs, and inflammatory mediators. In the gut and pancreas, MT responds mainly to Zn status. A brain isoform, MT-3, has a specific neuronal growth inhibitory activity, while MT-1 and MT-2 have more diverse functions related to their thiolate cluster structure. These include involvement in Zn homeostasis, protection against heavy metal (especially Cd) and oxidant damage, and metabolic regulation via Zn donation, sequestration, and/or redox control. A possible role for MT-4 is related to copper requirements in epithelial differentiating tissues. 

Mischke D. The complexity of gene families involved in epithelial differentiation Keratin genes and the epidermal differentiation complex. Subcell Biochem. 1998 31 71-104. 

Sata H, Hasegawa T, Abe Y, et al. Expression of E-cadherin in bone and soft tissue sarcomas A possible role in epithelial differentiation. Hum Pathol. 1999 30 1344-1349. 

Nutritional vitamin A deficiency causes xerophthalmia, a progressive disease characterized by night blindness, xerosis (dryness), and keratomalacia (comeal thinning), which may lead to perforation xerophthalmia may be reversed with vitamin A therapy. However, rapid, irreversible blindness ensues once the cornea perforates. Vitamin A also is involved in epithelial differentiation and may have some role in corneal epithelial wound healing. There is no evidence to support using topical vitamin A for keratoconjunctivitis sicca in the absence of a nutritional deficiency. 

The earliest morphological change in the sebaceous follicle is an abnormal follicular epithelial differentiation, which results in ductal hypercornification. Cornified cells in the upper section of the follicular canal become abnormally adherent. Comedones represent the retention of hyperproliferating ductal keratinoc-ytes in the duct. Several factors have been implicated in the induction of hyperproliferation sebaceous lipid composition, androgens, local cytokine production (IL-i, EGF) and bacteria (P. acnes). 

Vitamin A is essential throughout life, including foetal development, but perhaps its most well researched role is that in vision where 11 -cis retinaldehyde is the initial part of the photoreceptor complex in rods and cones. Retinoic acid induces differentiation in epithelial cells and deficiency leads to... 

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... 

Guillouzo et al. (1988) developed a coculture system of rat or human hepatocytes with rat liver epithelial cells that maintains the hepatocytes in a differentiated state for extended periods of time, thereby allowing studies involving chronic treatment with the test substance to be conducted. Primary cultures of hepatocytes can therefore provide a useful model for short- and long-term studies involving the safety assessment of xenobiotics. 

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). 

Polar Cell Systems for Membrane Transport Studies Direct current electrical measurement in epithelia steady-state and transient analysis, 171, 607 impedance analysis in tight epithelia, 171, 628 electrical impedance analysis of leaky epithelia theory, techniques, and leak artifact problems, 171, 642 patch-clamp experiments in epithelia activation by hormones or neurotransmitters, 171, 663 ionic permeation mechanisms in epithelia biionic potentials, dilution potentials, conductances, and streaming potentials, 171, 678 use of ionophores in epithelia characterizing membrane properties, 171, 715 cultures as epithelial models porous-bottom culture dishes for studying transport and differentiation, 171, 736 volume regulation in epithelia experimental approaches, 171, 744 scanning electrode localization of transport pathways in epithelial tissues, 171, 792. 

PPAR is a nuclear receptor-transcription factor and is ligand-dependent and expressed in several tissues. It is initially involved in adipocyte differentiation and fatty acid synthesis. Fatty acid and eicosanoids bind to PPAR and regulate transcription. PPAR activation inhibits monocyte differentiation and expression of several pro-inflammatory genes such as iNOS, TNF, etc. PPAR activation inhibits tumor cell proliferation (epithelial, colon, prostate). PPAR is involved in angiogenesis. 

Garcia Pedrero, J.M., Fernandez, M.P., Morgan, R.O., Herrero Zapatero, A., Gonzalez, M.V., Suarez Nieto, C., and J.P. Rodrigo, 2004, Annexin Al down-regulation in head and neck cancer is associated with epithelial differentiation status. Am J Pathol. 164(1) 73—9. 

Dong Y, Kaushal A, Brattsand M, Nicklin J, Clements JA. Differential splicing of KLK5 and KLK7 in epithelial ovarian cancer produces novel variants with potential as cancer biomarkers. Clin Cancer Res 2003 9 1710-1720. 

Behrens, J., Vakaet, L., Friis, R., Winterhager, E., Van Roy, F., et al. 1993. Loss of epithelial differentiation and gain of invasiveness correlates with tyrosine phosphorylation of the E-cadherin/beta-catenin complex in cehs transformed with a temperature-sensitive v-SRC gene. J. Cell Biol. 120 757-766. 

Cultures of isolated keratinocytes have facilitated the study of epithelial HA metabolism. Basal keratinocytes synthesize copious quantities of HA. When Ca++ of the culture medium is increased, from 0.05 to 1.20 mM, these cells begin to differentiate, HA synthesis levels drop,148 and there is an onset of hyaluronidase activity.149 This increase in calcium that appears to simulate in culture the natural in situ differentiation of basal keratinocytes parallels the increasing calcium gradient observed in the epidermis. There may be intracellular stores of calcium that are released as keratinocytes mature. 

Epithelial cells are interconnected at the apical (mucosal) side by a complex network of proteins, called the tight junctions (TJ). First thought to have merely a static role in restricting access of compounds present in the luminal fluid to the underlying subepithelial tissue and systemic circulation by the paracellular pathway, TJ are known today to be dynamic structures involved in cellular differentiation, cell signaling (Harder and Margolis 2008), polarized vesicle trafficking, and protein synthesis. 

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