Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 19 recordsLinked to original sources

PubMed2006

Upregulation of retinal transglutaminase during the axonal elongation stage of goldfish optic nerve regeneration.

Fish CNS neurons can repair their axons following nerve injury, whereas mammalian CNS neurons cannot regenerate, and become apoptotic within 1-2 weeks after the nerve lesion. One explanation for these differences is that one, or several molecules are upregulated in fish CNS neurons during nerve regeneration, and this same molecule is downregulated in mammalian CNS neurons before the development of apoptosis caused by nerve injury. A molecule satisfying these criteria might successfully rescue and repair the mammalian CNS neurons. In this study, we looked for such a candidate molecule from goldfish retinas. Transglutaminase derived from goldfish retina (TG(R)) was characterized as a regenerating molecule after optic nerve injury. A full-length cDNA for TG(R) was isolated from the goldfish retinal cDNA library prepared from axotomized retinas. Levels of TG(R) mRNA and protein increased only in the retinal ganglion cells (RGCs) between 10 and 40 days after optic nerve transection. Recombinant TG(R) protein enhanced neurite outgrowth from adult fish RGCs in culture. Specific interference RNA and antibodies for TG(R) inhibited neurite outgrowth both in vitro and in vivo. In contrast, the level of TG(R) protein decreased in rat RGCs within 1-3 days after nerve injury. Furthermore, the addition of recombinant TG(R) to retinal cultures induced striking neurite outgrowth from adult rat RGCs. These molecular and cellular data strongly suggest that TG(R) promotes axonal elongation at the surface of injured RGCs after optic nerve injury.

Animals↗

PubMed2006

Evidence of lymphangiogenesis in Warthin's tumor of the parotid gland.

The details of the pathogenesis of cystadenolymphoma (Warthin's tumor) of the parotid gland are still unclear. Neovascularization is considered to be a pivotal factor for solid tumor progression and biological behavior of the tumor. Using double-labeling immunohistochemistry for LYVE-1 and CD34 (specific markers for lymphatic and vascular endothelial cells, respectively) this study analyzes lymphatic vessel density (LVD) and blood vessel density (BVD) in 10 Warthin's tumors and 10 pleomorphic adenomas of the parotid gland as well as in 5 normal parotid glands and 5 normal parotid lymph nodes. There was no significant difference in the intratumoral LVD and BVD among pleomorphic adenoma and normal parotid gland tissue. In contrast, the intratumoral LVD and BVD were significantly higher in Warthin's tumor than pleomorphic adenoma, normal parotid gland and parotid lymph node (P<0.0001 versus P<0.004). The increase in lymphatic vessels in Warthin's tumor suggests that epithelial tumor cells might promote lymphangiogenesis in this kind of lesions.

Adenolymphoma↗

PubMed2006

Functional categories of TP53 mutation in colorectal cancer: results of an International Collaborative Study.

BACKGROUND: Loss of TP53 function through gene mutation is a critical event in the development and progression of many tumour types including colorectal cancer (CRC). In vitro studies have found considerable heterogeneity amongst different TP53 mutants in terms of their transactivating abilities. The aim of this work was to evaluate whether TP53 mutations classified as functionally inactive (< or=20% of wildtype transactivation ability) had different prognostic and predictive values in CRC compared with mutations that retained significant activity. MATERIALS AND METHODS: TP53 mutations within a large, international database of CRC (n = 3583) were classified according to functional status for transactivation. RESULTS: Inactive TP53 mutations were found in 29% of all CRCs and were more frequent in rectal (32%) than proximal colon (22%) tumours (P < 0.001). Higher frequencies of inactive TP53 mutations were also seen in advanced stage tumours (P = 0.0003) and in tumours with the poor prognostic features of vascular (P = 0.006) and lymphatic invasion (P = 0.002). Inactive TP53 mutations were associated with significantly worse outcome only in patients with Dukes' stage D tumours (RR = 1.71, 95%CI 1.25-2.33, P < 0.001). Patients with Dukes' C stage tumours appeared to gain a survival benefit from 5-fluorouracil-based chemotherapy regardless of TP53 functional status for transactivation ability. CONCLUSIONS: Mutations that inactivate the transactivational ability of TP53 are more frequent in advanced CRC and are associated with worse prognosis in this stage of disease.

Adenocarcinoma↗

PubMed2006

Monocarboxylate transporter 1 gene expression in the ovine gastrointestinal tract.

In this study, we investigated the tissue distribution and expression of monocarboxylate transporter 1 (MCT1) along the gastrointestinal tract of sheep. Western blot analysis suggested the presence of MCT1 as a 43-kDa protein in immunoblots of membranes from the various tissues examined. The results of Western blotting were further confirmed by immunohistochemical studies, which revealed intense immunoreactivity for the MCT1 protein in the forestomach (rumen, reticulum and omasum) and large intestine (caecum, proximal and distal colon). Moderate reactivity, however, was detected in the abomasum, while no immunoreactivity could be seen in any regions of the small intestine examined. Furthermore, MCT1 was expressed at the mRNA level as determined by reverse transcriptase polymerase chain reaction (RT-PCR), which showed a band of the expected size (300 bp) in all tissues examined. From these results we concluded that MCT1 protein is highly expressed and distributed in the stomach and large intestine of sheep suggesting that MCT1 may play a significant role in the transport of short chain fatty acids and their metabolites in the gastrointestinal tract of ruminants.

Animals↗

PubMed2006

Galanin-like peptide promotes feeding behaviour via activation of orexinergic neurones in the rat lateral hypothalamus.

Galanin-like peptide (GALP) is produced in neurones in the hypothalamic arcuate nucleus and is implicated in the neural control of feeding behaviour. Previously, we have reported that GALP immunoreactive fibres were in direct contact with orexin/hypocretin immunoreactive neurones in the rat lateral hypothalamus using double-immunofluorescence. Centrally administered GALP is known to stimulate feeding behaviour. However, the target neurones of this action have not been clarified. The present study aimed to determine features of the GALP-mediated neuronal feeding pathway in rat. Accordingly, at the ultrastructural level, GALP-immunoreactive axon terminals were found to make synapses on orexin/hypocretin immunoreactive cell bodies and dendritic processes in the lateral hypothalamus. c-Fos immunoreactivity was expressed in orexin/hypocretin-immunoreactive neurones but not in melanin concentrating hormone-immunoreactive neurones in the lateral hypothalamus at 90 min after the application of GALP by i.c.v. infusion. Furthermore, to determine whether GALP regulates feeding behaviour via orexin/hypocretin neurones, the feeding behaviour of rats was studied following GALP i.c.v. injection with or without anti-orexin A and B immunoglobulin (IgG) pretreatment. The anti-orexin IgGs markedly inhibited GALP-induced hyperphagia. These results suggest that orexin/hypocretin-containing neurones in the lateral hypothalamus are targeted by GALP, and that GALP-induced hyperphagia is mediated via orexin/hypocretin neurones in the rat hypothalamus.

Animals↗

PubMed2006

Detection of Lactobacillus gasseri OLL2716 strain administered with yogurt drink in gastric mucus layer in humans.

In animal models and human trials, Lactobacillus gasseri OLL2716 (LG21) strain suppressed Helicobacter pylori colonization in the stomach. The aim of the present study was to clarify whether orally administered LG21 strain can enter the gastric mucus layer. Biopsy samples were taken from the gastric antrum and corpus of two healthy volunteers (H. pylori infected and non-infected) who drank yogurt supplemented with LG21 strains. DNA of LG21 and H. pylori in the mucus layer was detected using the laser-assisted microdissection and non-contact pressure catapulting (LMPC) method and the semi-nested PCR method with primer sets of RNA helicases of superfamily II gene-Insertion sequence for LG21 strain and those of ureA gene for H. pylori. In the volunteer with H. pylori infection, DNA fragments of LG21- and H. pylori-specific regions from both antrum and corpus were amplified, whereas in a non-infected volunteer, only the LG21 DNA from the antrum was amplified. The present study demonstrated that LG21 strains administered through a yogurt drink can enter into the gastric mucus layer. Our novel method may be useful in studying gastric probiotics for H. pylori infection.

Gastric Mucosa↗

PubMed2006

Histological recovery of the hepatocytes is based on the redox system upregulation in the animal models of mutant superoxide dismutase (SOD)1-linked amyotrophic lateral sclerosis.

Histological rescue of superoxide dismutase1 (SOD1)-mutated hepatocytes from mutant SOD1 stress is investigated from the viewpoint of upregulation of the redox system [peroxiredoxin (Prx) and glutathione peroxidase (GPx)]. Histopathological and immunohistochemical studies using antibodies against PrxI/PrxII/GPxI were carried out on specimens from four different strains of animal models of mutant SOD1-linked familial amyotrophic lateral sclerosis (ALS). In the livers of the ALS animal models in the presymptomatic stage without motor neuron loss, both swollen and eosinophilic hepatocytes with vacuolation pathology were observed. After developing motor deficits, this swelling and vacuolation ceased to be apparent. In the terminal stage when severe motor neuron loss was observed, these hepatocytes recovered and appeared normal. In redox system-related immunohistochemical preparations, almost all of the normal hepatocytes expressed the redox system-related enzymes PrxI/PrxII/GPxI. In the presymptomatic stage, some hepatocytes did not express redox system-related enzymes. After clinical onset, over 75% of hepatocytes showed overexpression of PrxI/PrxII/GPxI, i. e., upregulation of the redox system. At the end stage, near normal PrxI/PrxII/GPxI expression was observed again in the hepatocytes. Redox system upregulation in SOD1-mutated hepatocytes rescues hepatocytes from the mutant SOD1 stress that leads to motor neuron death.

Amyotrophic Lateral Sclerosis↗

PubMed2005

Propionibacterium freudenreichii component 1.4-dihydroxy-2-naphthoic acid (DHNA) attenuates dextran sodium sulphate induced colitis by modulation of bacterial flora and lymphocyte homing.

BACKGROUND AND AIMS: 1.4-Dihydroxy-2-naphthoic acid (DHNA), a bifidogenic growth stimulator from Propionibacterium freudenreichii, is thought to have a beneficial effect as a prebiotic; however, its in vivo effect on intestinal inflammation remains unknown. The aim of this study was to determine whether oral administration of DHNA can ameliorate dextran sodium sulphate (DSS) induced colitis and to determine the possible underlying mechanisms. METHOD: Colitis was induced in mice by treatment with 2.0% DSS for seven days. DHNA (0.6 or 2.0 mg/kg) was given in drinking water prior to (preventive study) or after (therapeutic study) DSS administration. Colonic damage was histologically scored, and mucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression and beta7 positive cell infiltration were determined by immunohistochemistry. mRNA levels of proinflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumour necrosis factor alpha (TNF-alpha)) were determined by quantitative real time polymerase chain reaction. In addition, bacterial flora in the caecum, concentrations of short chain acids, and luminal pH were examined. RESULTS: DHNA improved survival rate and histological damage score in mice administered DSS in both the preventive and therapeutic studies. DHNA significantly attenuated the enhanced expression of MAdCAM-1, the increased beta7 positive cell number, and the increased mRNA levels of IL-1beta, IL-6, and TNF-alpha in DSS treated colon. In addition, the decreased number of Lactobacillus and Enterobacteriaceae induced by DSS was recovered by DHNA. Preventive effects on decrease in butyrate concentration and decrease in pH level in mice administered DSS were also observed in the DHNA preventive study. CONCLUSION: DHNA, a novel type of prebiotic, attenuates colonic inflammation not only by balancing intestinal bacterial flora but also by suppressing lymphocyte infiltration through reduction of MAdCAM-1.

Animals↗

PubMed2005

Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice.

BACKGROUND: While tumour necrosis factor alpha (TNF-alpha) appears to be associated with the development of non-alcoholic steatohepatitis (NASH), its precise role in the pathogenesis of NASH is not well understood. METHODS: Male mice deficient in both TNF receptors 1 (TNFR1) and 2 (TNFR2) (TNFRDKO mice) and wild-type mice were fed a methionine and choline deficient (MCD) diet or a control diet for eight weeks, maintaining isoenergetic intake. RESULTS: MCD dietary feeding of TNFRDKO mice for eight weeks resulted in attenuated liver steatosis and fibrosis compared with control wild-type mice. In the liver, the number of activated hepatic Kupffer cells recruited was significantly decreased in TNFRDKO mice after MCD dietary feeding. In addition, hepatic induction of TNF-alpha, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 was significantly suppressed in TNFRDKO mice. While in control animals MCD dietary feeding dramatically increased mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in both whole liver and hepatic stellate cells, concomitant with enhanced activation of hepatic stellate cells, both factors were significantly lower in TNFRDKO mice. In primary cultures, TNF-alpha administration enhanced TIMP-1 mRNA expression in activated hepatic stellate cells and suppressed apoptotic induction in activated hepatic stellate cells. Inhibition of TNF induced TIMP-1 upregulation by TIMP-1 specific siRNA reversed the apoptotic suppression seen in hepatic stellate cells. CONCLUSIONS: Enhancement of the TNF-alpha/TNFR mediated signalling pathway via activation of Kupffer cells in an autocrine or paracrine manner may be critically involved in the pathogenesis of liver fibrosis in this NASH animal model.

Animals↗

PubMed2005

Monocarboxylate transporter 1 (MCT1) in the liver of pre-ruminant and adult bovines.

This study investigated the distribution and expression of monocarboxylate transporter 1 (MCT1) in the livers of pre-ruminant calves and adult bovines (bulls and cows), using different molecular biological techniques. Reverse transcription-polymerase chain reaction (RT-PCR) verified the presence of mRNA encoding for MCT1 in both pre-ruminant and adult bovine livers. Immunohistochemically, MCT1 was clearly demonstrated on the sinusoidal surfaces of bovine hepatocytes but its expression varied widely between pre-ruminants and adult bovines. In pre-ruminants, a faint hepatocellular expression of MCT1 was observed in a few hepatocytes, whereas an intense immunoreactive staining for MCT1 was shown in the majority of adult bovine hepatocytes. Western blot analysis also confirmed the results of the immunohistochemistry. Quantitative immunoblotting, as estimated by densitometric analysis, showed that the level of MCT1 in the liver of adult bovines was 8-9-fold greater (P<0.01) than that in pre-ruminant calf livers although no significant differences were detected between bulls and cows. The results demonstrated that MCT1 may play a crucial role in the transport of propionate in bovine liver, suggesting that MCT1 expression may be influenced by developmental and metabolic regulations.

Aging↗

PubMed2005

The DNA mismatch repair gene hMSH2 is a potent coactivator of oestrogen receptor alpha.

The DNA mismatch repair gene is a key regulator in the elimination of base-base mismatches and insertion/deletion loops (IDLs). Human MutS homologue 2 (hMSH2), originally identified as a human homologue of the bacterial MutS, is a tumour suppressor gene frequently mutated in hereditary non-polyposis colorectal cancer. Hereditary non-polyposis colorectal cancer is characterised by the early onset of colorectal cancer and the development of extracolonic cancers such as endometrial, ovarian, and urological cancers. Oestrogen receptor (ER) alpha and beta are members of a nuclear receptor (NR) superfamily. Ligand-dependent transcription of ER is regulated by the p160 steroid receptor coactivator family, the thyroid hormone receptor-associated proteins/the vitamin D receptor-interacting proteins (TRAP/DRIP) mediator complex, and the TATA box-binding protein (TBP)-free TBP associated factor complex (TFTC) type histone acetyltransferase complex. Here, we report the interaction between ER alpha/beta and hMSH2. Immunoprecipitation and glutathione-S-transferase pull-down assay revealed that ER alpha and hMSH2 interacted in a ligand-dependent manner, whereas ER beta and hMSH2 interacted in a ligand-independent manner. Oestrogen receptor alpha/beta bound to hMSH2 through the hMSH3/hMSH6 interaction domain of hMSH2. In a transient expression assay, hMSH2 potentiated the transactivation function of liganded ER alpha, but not that of ER beta. These results suggest that hMSH2 may play an important role as a putative coactivator in ER alpha dependent gene expression.

Base Pair Mismatch↗

PubMed2005

Expression and distribution of monocarboxylate transporter 1 (MCT1) in the gastrointestinal tract of calves.

In the present study the expression and distribution of monocarboxylate transporter 1 (MCT1) along the gastrointestinal tract (rumen, reticulum, omasum, abomasum, duodenum, jejunum, ileum, cecum and colon) of calves were investigated on both mRNA and protein levels. The expression of MCT1 protein and its distribution were determined by Western blotting and immunohistochemical staining, respectively by using antibody for MCT1. MCT1 protein was visualized as a 43-kDa band on immunoblots of the membrane proteins prepared from the various regions examined, and it was more highly expressed in forestomach and large intestine than in abomasum and small intestine. With the use of reverse transcriptase-polymerase chain reaction, mRNA encoding for MCT1 was demonstrated in the different tissues examined. The immunohistochemical study confirmed the Western blot findings and showed strong MCT1 immunopositive staining in the stratified squamous epithelia of the forestomach as well as the epithelial cells lining the digestive tract in the cecum, proximal colon, and distal colon. The results suggest that MCT1 may play a role in the transport of SCFA and their metabolites in the gastrointestinal tract of bovines.

Amino Acid Sequence↗

PubMed2005

Progesterone pre-treatment potentiates EGF pathway signaling in the breast cancer cell line ZR-75.

Progesterone in hormone replacement therapy (HRT) preparations increases, while hysterectomy greatly reduces, the incidence of breast cancer. Cross-talk between the progesterone and growth factor signaling pathways occurs at multiple levels and this maybe a key factor in breast cancer survival and progression. To test this hypothesis, we characterized the effect of progesterone pre-treatment on the sensitization of the epidermal growth factor (EGF) signaling pathway to EGF in the breast cancer cell line ZR-75. For the first time in ZR-75 cells and in agreement with previous work using synthetic progestins, we demonstrate that pre-treatment with the natural ligand progesterone increases EGF receptor (EGFR) levels and subsequent ligand-dependent phosphorylation. Downstream we demonstrate that progesterone alone increases erk-1 + 2 phosphorylation, potentiates EGF-phosphorylated erk-1 + 2 and maintains these levels elevated for 24 h; over 20 h longer than in vehicle treated cells. Additionally, progesterone increased the levels of STAT5, another component of the EGF signaling cascade. Progesterone increased EGF mediated transcription of a c-fos promoter reporter and the nuclear localization of the native c-fos protein. Furthermore, progesterone and EGF both alone and in combination, significantly increase cell proliferation. Several results presented herein demonstrate the conformity between the action of the natural ligand progesterone with that of synthetic progestins such as MPA and R5020 and allows the postulation that the progestin/progesterone-dependent increase of EGF signaling provides a survival advantage to burgeoning cancer cells and may contribute to the breast cancer risk associated with endogenous progesterone and with progestin-containing HRT.

Breast Neoplasms↗

PubMed2005

Blinking and superficial punctate keratopathy in patients with diabetes mellitus.

AIM: To evaluate blinking patterns in patients with diabetes mellitus and whether blinking contributes to the formation of superficial punctate keratopathy in diabetic patients. METHODS: We examined 163 patients with type II diabetes mellitus and 76 without diabetes. Blinks were recorded, analysed using six parameters, and compared between patients with and without diabetes. Multivariate regression analysis was performed to assess the influence of other ocular factors, such as status of tear lipid layer, tear breakup time, corneal sensitivity, the result of cotton thread test, or blinking rate related to superficial punctate keratopathy. RESULTS: In patients with diabetes, the average mean and maximum interblinking times were longer, the average coefficient of variation of interblinking time was higher, and the average blinking rates were lower than those in patients without diabetes. Multivariate regression analysis revealed that the status of tear lipid layer and tear breakup time were significantly relevant to superficial punctate keratopathy (P < 0.01). CONCLUSION: Interblinking time was longer in diabetic patients, resulting in a decreased blinking rate. The prevalence of superficial punctate keratopathy cannot be predicted from blinking patterns in patients with diabetes.

Aged↗

PubMed2005

Value of chemotherapy before allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor for myelodysplastic syndrome.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a curative treatment for myelodysplastic syndrome (MDS). The object of this study was to evaluate the impact of chemotherapy before allo-SCT. We analyzed the data of 283 patients who underwent allo-SCT from an HLA-identical sibling donor for MDS that were reported to the Japan Society for Hematopoietic Cell Transplantation. The cumulative incidence of grade II-IV acute GVHD was 33%. Overall survival (OS) at 5 and 10 years was 48.8 and 42.5%, respectively. Multivariate analyses identified karyotype, FAB classification, and the history of chemotherapy before allo-SCT as significant predictors for OS. OS at 5 years was 57% for patients who underwent allo-SCT as a primary treatment for refractory anemia with excess blasts in transformation (RAEB-t) or secondary acute myeloid leukemia (AML) and 54% for those who underwent allo-SCT in remission after induction chemotherapy (P=0.81). The proportion of patients with a poor karyotype was equivalent between the two groups (P=0.44). Although only a randomized controlled trial will be able to establish a definite conclusion, these results do not support the administration of induction chemotherapy for patients with RAEB-t or secondary AML before allo-SCT.

Adolescent↗

PubMed2005

Image-guided stereotactic radiosurgery with the CyberKnife for pituitary adenomas.

This study demonstrates the clinical usefulness of image-guided fractionated stereotactic radiosurgery with the CyberKnife system. Twenty-one patients with pituitary adenomas received image-guided stereotactic radiosurgery with the CyberKnife, and were followed up for more than 18 months. The patients consisted of 14 with non-functioning adenomas, 3 with prolactinomas, 2 with acromegaly, and 2 with ACTH-producing tumors. In 20 cases, fractionated radiosurgery was performed. The change in the tumor volume, visual acuity, hormonal function, and complications by this therapy were analyzed in each case. The volume of the tumors ranged from 0.2 cm (3) to 34.9 cm (3) (mean +/- SD: 11.3 +/- 9.2 cm (3)). The mean volumes of the non-functioning and functioning adenomas were 13.3 cm (3) and 7.5 cm (3), respectively. The marginal irradiation dose ranged from 6.4 Gy to 27.7 Gy (mean: non-functioning adenomas 12.6 Gy, functioning adenomas 17.5 Gy), as a dose of a single fraction. The follow-up periods ranged from 18 months to 59 months (mean +/- SD: 35.3 +/- 10.7 months). The tumor control rate was 95.2 %. In 1 case, visual acuity worsened due to cystic enlargement of the tumor. Hormonal function improved in all of the 7 functioning adenomas. The hormone level normalized in 1 prolactinoma, and decreased to less than normal in 1 ACTH-producing adenoma. In 2 cases, hypopituitarism occurred after the therapy. Image-guided stereotactic radiosurgery with the CyberKnife is effective and safe against relatively large pituitary adenomas. Careful long-term follow-up of the patients is necessary because of delayed cystic enlargement of the tumor in rare cases.

Adenoma↗

PubMed2005

Vitamin D receptor ablation alters skin architecture and homeostasis of dendritic epidermal T cells.

BACKGROUND: 1alpha,25-dihydroxyvitamin D(3)[1,25(OH)(2)D(3)], the active metabolite of vitamin D, exerts its activities by binding to the vitamin D receptor (VDR) with subsequent function as a transcription factor. Targeted ablation of the VDR in mice results in rickets and alopecia. OBJECTIVES: To study the consequences of VDR deficiency for skin physiology, and to investigate the mechanisms of the immunosuppressive effect of 1,25(OH)(2)D(3) on LC. METHODS: We studied the structural, phenotypic and functional properties of skin and individual skin leucocyte populations in VDR(-/-) mice. RESULTS: The lack of VDR induced a wide spectrum of pathologies including dermal deposition of collagen, enlargement of sebaceous glands, dilation of the hair follicles, development of epidermal cysts, increased numbers of dendritic epidermal T cells (DETC) and hyperkeratosis. Ageing aggravated these changes. Intriguingly, Langerhans cells (LC) were indistinguishable in distribution, morphology and number compared with controls. In vitro, LC underwent a maturation/migration process similar to LC from control mice. Pretreatment of epidermal cells or LC-enriched epidermal cell suspensions with 1,25(OH)(2)D(3) impaired LC maturation and T-cell stimulatory capacity from VDR(+/+) but not VDR(-/-) mice, demonstrating that LC are targets of vitamin D(3) and that interaction between vitamin D(3) and LC results in a suppression of LC activity. CONCLUSIONS: Our data imply that VDR expression controls dermal collagen production, hair development and growth, proliferation of sebaceous glands and the homeostasis of DETC. Surprisingly, VDR deficiency does not influence LC phenotype and function.

Aging↗

PubMed2005

N-retinoyl-D-glucosamine, a new retinoic acid agonist, mediates topical retinoid efficacy with no irritation on photoaged skin.

BACKGROUND: Chronic ultraviolet (UV) radiation from sunlight induces wrinkle formation. Retinoic acid (RA) can markedly improve wrinkles, although RA does have some side-effects, such as skin irritation. As the efficacy and cytotoxicity of RA has been traced to its free carboxylic acid, we synthesized a new molecule, N-retinoyl-D-glucosamine (GRA), in which a glucosamine has been attached to the polar end group of all-trans retinoic acid. OBJECTIVES: To analyse the effect of topical GRA in wrinkle repair and anti-irritation in photoaged mice compared with topical RA, as well as to determine retinoic acid receptor (RAR) and retinoid X receptor (RXR) transactivation activity in vitro. METHODS: Hairless mice were irradiated with 60 mJ cm-2 of UVB for 10 weeks, and then topically treated with 0.05% GRA or 0.05% RA for 8 weeks. An in vitro transcriptional assay was performed and the activity of GRA in 293 cells transfected with RAR-alpha or RXR-alpha expression plasmid and luciferase reporter plasmid then determined. RESULTS: Topical GRA and RA brought about almost complete disappearance of the wrinkles caused by UVB irradiation. The two ligands promoted both a wide repair zone histologically, and the expression of type 1 collagen in the skin. In contrast, topical GRA treatment did not produce irritation such as erythema or roughness, or alteration of transepidermal water loss values, compared with RA. In the in vitro luciferase assay, GRA resulted in significant dose-dependent RAR transactivation activity in a 100 times higher concentration range than RA. GRA did not mediate RXR transactivation activity at all. CONCLUSIONS: Topical GRA appears to be able to repair photoaged skin damage without any of the irritation caused by topical RA, probably via RAR transactivation activity.

Administration, Topical↗