Paper
Alterations in Mouse Epidermal Keratin Production Induced by Dietary Vitamin A Deficiency a
Published Oct 1, 1985 · C. Molloy, J. Laskin
Annals of the New York Academy of Sciences
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Abstract
Vitamin A is a naturally occurring fat-soluble compound that has been recognized as an important dietary component for over 50 years.' It plays an essential role in normal mammalian development and metabolism.2 Vitamin A also has profound effects on cell growth and differentiation and is required for the formation and integrity of all epithelial tissue^.^ Vitamin A deficiency in rodents leads to growth retardation, weight loss, and abnormal changes in many organs including trachea, skin, testes, and ovaries! Normal differentiation of stem cells into mature epithelial cells is inhibited and metaplasia, characterized by excessive accumulation of keratin, is frequently observed in these animals3 In normal epidermis, keratinocytes undergo differentiation as they mature from basal cells to stratum corneum. This process is characterized by specific morphologic and biochemical changes that include the appearance of keratohyaline granules, the formation of insoluble cornified envelopes, and the expression of specific keratins? In the present study, we have examined the effects of prolonged dietary vitamin A deficiency on the production of keratins in mouse epidermis. Pregnant CF-1 mice were fed either a normal diet or one deficient in vitamin A (US Biochemical Corp). At birth, litters were sorted and pups in the vitamin A-deficient group were maintained on this diet. After 10 weeks, the dorsal skin of mice in both groups was depilated and pulse-labeled by floating excised skin on cell culture medium supplemented with [35S]methionine. After labeling, pure epidermis was harvested, solubilized, and the keratins were separated by two-dimensional gel electrophoresis. Gels were either stained with silver to determine the total proteins present, or autoradiographed to analyze newly synthesized proteins. We have previously shown that epidermal cells from skin readily incorporate [3sS]methionine and radiolabeled proteins can be resolved using these techniques? We found that over 200 individual proteins from the epidermis could be resolved in gels from both control and vitamin A-deficient mice. Gels, whether stained or autoradiographed, were found to have similar protein profiles. The proteins present in the greatest abundance were the keratins appearing in the 45-65K molecular weight
Prolonged dietary vitamin A deficiency in mice leads to altered keratin production, affecting skin development and keratin production.
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