Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P05109 (S100A8)
 1,212 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

S100A2 is a homodimeric protein that undergoes oxidative cross-linking and translocation from the nucleus to the cytosol in the context of oxidative stress. Suggestive of a role for S100A2 in the cutaneous response to ultraviolet light, we found altered S100A2 immunostaining in photodamaged human skin, and crosslinking of S100A2 after ultraviolet A (UVA) irradiation of normal human keratinocytes (NHK). Skin from mice, rats, and rabbits did not contain S100A2 protein, whereas skin samples from pigs, frogs and humans were strongly positive. Survival after UVA irradiation was significantly greater in NHK compared to mouse keratinocytes, suggesting a protective role for S100A2. To test this hypothesis in vivo, we expressed S100A2 in SKH2/J hairless mice under the control of a bovine keratin 5 promoter, and compared responses of TG and WT mice from 1 to 7 days after a single dose (0.5-1 MED) of solar-simulated radiation (SSR) from UVA-340 bulbs. WT and TG mice manifested a similarly robust response to SSR, characterized by epidermal hyperplasia, marked induction of p21(WAF), and a twofold increase in p53. Thymine dimers (TD) were markedly increased in the epidermis and the dermis, but while over 95% of the epidermal TD were removed by 5-6 days, elevated dermal TD persisted nearly unchanged for 7 days. Global transcriptional profiling of WT and TG mice revealed strong induction of multiple transcripts, including keratins K6 and K16, defensin beta 3, S100A8, S100A9, Sprr2i and Sprr2f. However, the only S100A2-dependent difference we observed was an induction of Cxcl13 transcripts in TG, but not WT mice (4.4-fold vs. 0.7-fold, n = 3, P = 0.022). This finding was confirmed in an independent set of mice analyzed by quantitative RT-PCR (8.8-fold vs. 1.2-fold, n = 4, P = 0.001). The finding of persistent dermal DNA damage after suberythemal doses of SSR merits further study.
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PMID:Transgenic expression of S100A2 in hairless mouse skin enhances Cxcl13 mRNA in response to solar-simulated radiation. 1877 13

The nuclear vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D3 (1,25D), its high affinity renal endocrine ligand, to signal intestinal calcium and phosphate absorption plus bone remodeling, generating a mineralized skeleton free of rickets/osteomalacia with a reduced risk of osteoporotic fractures. 1,25D/VDR signaling regulates the expression of TRPV6, BGP, SPP1, LRP5, RANKL and OPG, while achieving feedback control of mineral ions to prevent age-related ectopic calcification by governing CYP24A1, PTH, FGF23, PHEX, and klotho transcription. Vitamin D also elicits numerous intracrine actions when circulating 25-hydroxyvitamin D3, the metabolite reflecting vitamin D status, is converted to 1,25D locally by extrarenal CYP27B1, and binds VDR to promote immunoregulation, antimicrobial defense, xenobiotic detoxification, anti-inflammatory/anticancer actions and cardiovascular benefits. VDR also affects Wnt signaling through direct interaction with beta-catenin, ligand-dependently blunting beta-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating beta-catenin signaling via VDR ligand-independent mechanisms in osteoblasts and keratinocytes to function osteogenically and as a pro-hair cycling receptor, respectively. Finally, VDR also drives the mammalian hair cycle in conjunction with the hairless corepressor by repressing SOSTDC1, S100A8/S100A9, and PTHrP. Hair provides a shield against UV-induced skin damage and cancer in terrestrial mammals, illuminating another function of VDR that facilitates healthful aging.
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PMID:The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the "Fountain of Youth" to mediate healthful aging. 2022 97