Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0849640 (skin damage)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinoids provide some protection against ultraviolet radiation-induced skin damage. We have previously shown that topical all-trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of immunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all-trans retinoic acid to modulate Langerhans cell induction of allogeneic T-cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all-trans retinoic acid-treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte-macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell-stimulating capability of Langerhans cells isolated from ultraviolet-irradiated mice. Langerhans cells from all-trans retinoic acid-treated, ultraviolet-irradiated mice which were "matured" by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all-trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell-stimulating capacity. However, these mice remained immunosuppressed upon application of a contact sensitizer to irradiated or unirradiated skin. It is thus likely that, whereas all-trans retinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation-induced photoproduct which causes immunosuppression.
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PMID:All-trans retinoic acid induces functional maturation of epidermal Langerhans cells and protects their accessory function from ultraviolet radiation. 788 65

The carboxylic acids include alpha-hydroxyacids (AHAs), polyhydroxy acids (PHAs), aldobionic acids (ABAs), retinoic acid, vitamin C and azelaic acid. They all have therapeutic actions. AHAs, PHAs and ABAs are organic hydroxyacids, a group of natural and physiological substances which can modulate skin keratinization and increase biosynthesis of dermal components. Because of these effects, AHAs, PHAs and ABAs are therapeutically effective or beneficial for topical treatment of dry skin, rough skin, acne, rosacea, warts, eczema, psoriasis and skin changes associated with ageing, including wrinkles and photoageing. In addition, PHAs and ABAs, which are antioxidants, are topically beneficial for sensitive or diseased skin and for the prevention of oxidative damage caused by UV radiation. The vitamin A derivatives, known as retinoids, include three that are found physiologically. Retinoic acid is the most potent of these in promoting proliferation and differentiation of epithelial cells, and in stimulating biosynthesis of collagen I and III. Because of these actions, retinoic acid is therapeutically effective for topical treatment of acne, actinic keratoses and photoaged skin. Vitamin C, which is l-ascorbic acid and a lactone form of 3-keto-polyhydroxy acid, is a water-soluble antioxidant. Because of this property vitamin C has been promoted for topical prevention of skin damage caused by UV radiation. Azelaic acid has been shown to normalize keratinization in the follicular infundibulum, exert an antibacterial effect against Propionibacterium acnes and inhibit melanogenesis and so has been used for topical treatment of acne and melasma. The carboxylic acids display similarities and differences in their topical actions and therapeutic applications.
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PMID:Alpha-hydroxyacids and carboxylic acids. 1714 60

Retinoic acid (RA) has been widely used to protect skin from photo damage and skin carcinomas caused by solar ultraviolet (UV) irradiation, yet the mechanism remains elusive. Here, we report that all-trans retinoic acid (tRA) can directly induce the expression of a newly identified potent anti-angiogenic factor, seryl tRNA synthetase (SerRS), whose angiostatic role can, however, be inhibited by UV-activated ataxia telangiectasia mutated (ATM) kinase. In both a human epidermal cell line, HaCaT, and a mouse melanoma B16F10 cell line, we found that tRA could activate SerRS transcription through binding with the SerRS promoter. However, UV irradiation induced activation of ATM-phosphorylated SerRS, leading to the inactivation of SerRS as a transcriptional repressor of vascular endothelial growth factor A (VEGFA), which dampened the effect of tRA. When combined with ATM inhibitor KU-55933, tRA showed a greatly enhanced efficiency in inhibiting VEGFA expression and a much better protection of mouse skin from photo damage. Also, we found the combination greatly inhibited tumor angiogenesis and growth in mouse melanoma xenograft in vivo. Taken together, tRA combined with an ATM inhibitor can greatly enhance the anti-angiogenic activity of SerRS under UV irradiation and could be a better strategy in protecting skin from angiogenesis-associated skin damage and melanoma caused by UV radiation.
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PMID:Targeting Angiogenesis by Blocking the ATM-SerRS-VEGFA Pathway for UV-Induced Skin Photodamage and Melanoma Growth. 3176 90