检索结果-内蒙古大学图书馆

Coagulation factors VIIa and Xa induce cell signaling leading to up-regulation of the egr-1 gene

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第45期274卷 32225-32233页

作者： Camerer, E Rottingen, JA Gjernes, E Larsen, K Skartlien, AH Iversen, JG Prydz, H Ctr Biotechnol N-0371 Oslo Norway Univ Oslo Inst Basic Med Sci Dept Physiol Lab Intracellular Signaling N-0371 Oslo Norway

Intracellular signaling induced by the coagulation factors (F) VIIa and Xa is poorly understood. We report here studies on these processes in a human keratinocyte line (HaCaT), which is a constitutive producer of tissue factor (TF) and responds to both FVIIa and FXa with elevation of cytosolic Ca2+, phosphorylation of extracellular signal-regulated kinase (Erk) 1/2, p38(MAPK), and c-Jun N-terminal kinase, and up-regulation of transcription of the early growth response gene-1 (egr-1). Using egr-1 as end point, we observed with both agonists that phosphatidylinositol-specific phospholipase C and the mitogen-activated protein kinase/Erk kinase/Erk pathway were mediators of the responses. The responses to FVIIa were TF-dependent and up-regulation of egr-1 mRNA did not require presence of the TF cytoplasmic domain. Antibodies to EPR-1 and factor V had no effect on the response to FXa. We have provided evidence that TF is not the sole component of the FVIIa receptor. The requirement for proteolytic activity of both FVIIa and FXa suggests that protease-activated receptors may be involved. We now report evidence suggesting that protease-activated receptor 2 or a close homologue may be a necessary but not sufficient component of this particular signal transduction pathway. The up-regulation of egr-1 describes one way by which the initiation of blood coagulation may influence gene transcription. The ability of these coagulation proteases to induce intracellular signals at concentrations at or below the plasma concentrations of their zymogen precursors suggests that these processes may occur also in vivo.

关键词：钙/代谢细胞间通讯细胞培养的 DNA结合蛋白质类/生物合成 DNA结合蛋白质类/遗传学早期生长反应蛋白质1 因子Ⅶa/生理学因子Ⅹa/生理学即早蛋白质类角蛋白细胞/药物作用角蛋白细胞/生理学 RNA 信使/代谢转录因子/生物合成转录因子/遗传学增量调节毒力因子鲍特菌属/药理学动物狗人类

来源：评论

学校读者我要写书评

暂无评论

Activation of epidermal growth factor receptor promotes late terminal differentiation of cell-matrix interaction-disrupted keratinocytes

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 1999年第52期274卷 37285-37291页

作者： Wakita, N Takigawa, M Hamamatsu Univ Sch Med Dept Dermatol Hamamatsu Shizuoka 4313192 Japan

The biological effects of epidermal growth factor receptor (EGFR) activation may differ between epidermal suprabasal and basal keratinocytes, since growth factors are mitogenic in adherent cells only in the presence of cell-extracellular matrix (ECM) interaction, To investigate biological effects of EGFR activation on keratinocytes without cell-ECM interaction, we cultured normal human keratinocytes on polyhydroxyethyl-methacrylate-coated plates, which disrupt cell-ECM but not cell-cell interaction. The cells initially expressed keratin 10 (K10) and then profilaggrin, mimicking sequential differentiation of epidermal suprabasal keratinocytes, The addition of EGF or transforming growth factor-alpha promoted late terminal differentiation (profilaggrin expression, type 1 transglutaminase expression and activity, and cornified envelope formation) of the suspended keratinocytes, while suppressing K10 expression, an early: differentiation marker. These effects were attenuated by EGFR tyrosine kinase inhibitor PD153035 or an anti-EGFR monoclonal antibody, whereas protein kinase C inhibitors H7 and bisindolylmaleimide I or mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD98059 abolished profilaggrin up-regulation but not K10 suppression. Since the antidifferentiative role of EGFR on cell-ECM interaction-conserved keratinocytes has been well documented, our results indicate that the biological effects of EGFR:on keratinocytes are influenced by cell-ECM interaction and suggest that EGFR activation promotes rather than inhibits the terminal differentiation of suprabasal epidermal keratinocytes.

关键词： 1-(5-异喹啉磺酰基)-2-甲基哌嗪/药理学细胞分化/药物作用细胞培养的酶激活表皮生长因子/药理学细胞外基质/生理学类黄酮物质/药理学中间丝蛋白质类/生物合成角蛋白细胞/生理学角蛋白质类/生物合成蛋白激酶C/生理学蛋白质前体/生物合成转谷酰胺酶/生物合成动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

The calcium sensing receptor and its alternatively spliced form in murine epidermal differentiation

引用

JOURNAL OF BIOLOGICAL CHEMISTRY 2000年第2期275卷 1183-1190页

作者： Oda, Y Tu, CL Chang, WH Crumrine, D Kömüves, L Mauro, T Elias, PM Bikle, DD Univ Calif San Francisco Vet Affairs Med Ctr Dept Med & Dermatol San Francisco CA 94121 USA Univ Calif San Francisco Vet Affairs Med Ctr Dept Endocrinol San Francisco CA 94121 USA

We have recently reported that human keratinocytes express both the full-length calcium sensing receptor (CaR) and an alternatively spliced form lacking exon 5, which were suggested to be involved in calcium induced keratinocyte differentiation. To understand further the role of these CaRs, we analyzed the structure of mouse CaRs, and investigated their role using a mouse model in which only the full-length CaR was disrupted. Our results show that both the full-length and the alternatively spliced variant lacking exon 5 encoding 77 amino acids of the extracellular domain were expressed in mouse epidermis. The deletion of the full-length CaR increased the production of the alternatively spliced form of CaR in mutant mice. The keratinocytes derived from these mutant mice did not respond to extracellular calcium, suggesting that the full-length CaR is required to mediate calcium signaling in the keratinocytes. The loss of the full-length CaR altered the morphologic appearance of the epidermis and resulted in a reduction of the mRNA and protein levels of the keratinocyte differentiation marker, loricrin. These results indicate that CaR is important in epidermal differentiation, and that the alternatively spliced form does not fully compensate for loss of the full-length CaR.

关键词：选择性剪接氨基酸序列动物新生碱基序列钙/代谢细胞分化细胞系细胞培养的克隆分子表皮/生理学角蛋白细胞/细胞学角蛋白细胞/生理学小鼠基因敲除分子序列数据受体钙敏感受体细胞表面/化学受体细胞表面/遗传学受体细胞表面/生理学重组蛋白质类/化学重组蛋白质类/代谢逆转录聚合酶链反应序列比对序列同源性氨基酸皮肤/细胞学皮肤/代谢转染动物牛人类小鼠

来源：评论

学校读者我要写书评

暂无评论

Prolactin and its receptor are expressed in murine hair follicle epithelium, show hair cycle-dependent expression, and induce catagen

引用

AMERICAN JOURNAL OF PATHOLOGY 2003年第5期162卷 1611-1621页

作者： Foitzik, K Krause, K Nixon, AJ Ford, CA Ohnemus, U Pearson, AJ Paus, R Univ Hamburg Hosp Eppendorf Dept Dermatol D-20246 Hamburg Germany Ruakura Agr Res Ctr AgRes Hamilton New Zealand ViaLactia BioSci Auckland New Zealand

Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp and report that both PRL and PRLR are stringently restricted to the hair follicle epithelium and are strongly hair cycle-dependent. In addition we show that PRL exerts functional effects on anagen hair follicles in murine skin organ culture by down-regulation of proliferation in follicular keratinocytes. In telogen follicles, PRL-like immunoreactivity was detected in outer root sheath (ORS) keratinocytes. During early anagen (III to IV), the developing inner root sheath (IRS) and the surrounding ORS were positive for PRL. In later anagen stages, PRL could be detected in the proximal IRS and the inner layer of the ORS. The regressing (catagen) follicle showed a strong expression of PRL in the proximal ORS. In early anagen, PRLR immunoreactivity occurred in the distal part of the ORS around the developing IRS, and subsequently to a restricted area of the more distal ORS during later anagen stages and during early catagen. The dermal papilla (DP) stayed negative for both PRL and PRLR throughout the cycle. Telogen follicles showed only a very weak PRLR staining of ORS keratinocytes. The long-form PRLR transcript was shown by real-time polymerase chain reaction to be transiently down-regulated during early anagen, whereas PRL transcripts were up-regulated during mid anagen. Addition of PILL (400 ng/ml) to anagen hair follicles in murine skin organ culture for 72 hours induced premature catagen development in vitro along with a decline in the number of proliferating hair bulb keratinocytes. These data support the intriguing concept that PRL is generated locally in the hair follicle epithelium and acts directly in an autocrine or paracrine manner to modulate the hair cycle.

关键词：碱基序列细胞周期/生理学 DNA引物上皮细胞/细胞学上皮细胞/生理学基因表达调控毛发/细胞学毛发/生长和发育毛囊/细胞学毛囊/生理学角蛋白细胞/细胞学角蛋白细胞/生理学小鼠近交C57BL 模型动物胎盘催乳激素/遗传学聚合酶链反应催乳素/遗传学受体催乳素/遗传学皮肤/细胞学动物女(雌)性人类小鼠

来源：评论

学校读者我要写书评

暂无评论

Effect of N-acetylcysteine on UVB-induced apoptosis and DNA repair in human and mouse keratinocytes

引用

PHOTOCHEMISTRY AND PHOTOBIOLOGY 1999年第3期70卷 329-333页

作者： Bush, JA Ho, VC Mitchell, DL Tron, VA Li, G Univ British Columbia Vancouver Hosp & Hlth Sci Ctr Div Dermatol Dept Med Vancouver BC V5Z 1M9 Canada Univ Houston MD Anderson Canc Ctr Houston TX USA Univ British Columbia Dept Pathol Vancouver Hosp & Hlth Sci Ctr Vancouver BC Canada

The incidence of skin cancer is increasing rapidly, particularly in the Caucasian population. Epidemiological and experimental studies demonstrated that ultraviolet radiation (UVR) is the primary cause for the increasing incidence of skin cancer. It is well known that UV irradiation induces DNA damage. If the damage is not repaired or removed in time, it can lead to mutations and skin carcinogenesis. N-acetylcysteine (NAC) has been shown to be an effective protector against UVB induced immunosuppression and to modulate the expression elf some oncogenes and tumor suppressor genes. To test further the protective effect of NAC against UVR, we used both in vitro and in vivo models to investigate the effect of NAC on UVB-induced apoptosis and repair of DNA damage in human and mouse keratinocytes. Our data indicate that the intracellular glutathione level was inc creased after treatment with NAC at 10-20 mM but decreased with 40 mM NAC treatment due to the toxicity. At concentrations up to 20 mM NAC did not have a significant effect on UVB-induced apoptosis of cultured human keratinocytes, In addition, in an in vivo mouse model, topical application of NAC (3 mu mol cm(-2)) that has been shown to inhibit UVB-induced immunosuppression did not have any effect on UVB-induced apoptosis and did not reduce the formation or enhance the repair of UVB-induced cyclobutane pyrimidine dimers and (6-4) photoproducts, Our results indicate that NAC is ineffective in preserving the genomic stability of keratinocytes against UVB irradiation.

关键词：乙酰半胱氨酸/药理学细胞凋亡/药物作用细胞凋亡/辐射效应细胞存活/药物作用细胞存活/辐射效应细胞培养的 DNA/辐射效应 DNA损伤 DNA修复/药物作用 DNA修复/辐射效应谷胱甘肽/代谢角蛋白细胞/药物作用角蛋白细胞/代谢角蛋白细胞/生理学角蛋白细胞/辐射效应小鼠近交C57BL 紫外线动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

Proliferation in murine epidermis after minor mechanical stimulation -: Part 1.: Sustained increase in keratinocyte production and migration

引用

CELL PROLIFERATION 2000年第4期33卷 231-246页

作者： Potten, CS Barthel, D Li, YQ Ohlrich, R Matthé, B Loeffler, M Christie Hosp Paterson Inst Canc Res CRC Epithelial Biol Grp Manchester M20 4BX Lancs England Univ Leipzig Inst Med Informat Stat & Epidemiol D-7010 Leipzig Germany

It was our objective to obtain an insight into the details and dynamics of the cell proliferative changes following minor barrier disruption, the mechanisms of recovery, and their regulation. Hair of the dorsal area of DBA2-mice was removed and the epidermis was tape stripped. Tritiated thymidine was injected into groups of mice at daily intervals thereafter. Labelling and nuclear densities were measured at several time intervals later in the various epidermal strata to characterize cell production and cell fluxes through the tissue. A dramatic proliferative response was observed at 24 h when the labelling density increased more than sixfold in the basal layer. Labelled cells rapidly appeared in suprabasal layers within a few hours in large quantities while this process took over 2 days in normal skin. Some cycling cells were also found in the suprabasal layer (pulse labelling at 24 h) in contrast with the controls. The cellular flux through the suprabasal layers was drastically (20-fold) increased and the transit time was shortened. Although the nuclear density in the basal layer showed only moderate changes it increased four-fold in the suprabasal layer within 5 days. A kinetic model analysis suggested that the cell cycle time of proliferative cells dropped from a normal value of about 200 h to less than 12 h post tape strip, After 7 days, the proliferative activation still persisted, even though at 3 days post tape strip the stratum corneum had been reestablished. Hence, a mild mechanical alteration with removal of some parts of the cornified layer in mouse backskin epidermis triggers a huge proliferative response with massive overproduction of cells that lasts at least 7 days. Our findings suggest that the re-establishment of the cornified layer does not immediately shut down cell proliferation and that more complex, slower (long-term) regulatory processes are involved.

关键词：细胞计数细胞分裂细胞运动/生理学角蛋白细胞/细胞学角蛋白细胞/生理学动力学小鼠近交DBA 物理刺激时间因素动物男(雄)性小鼠

来源：评论

学校读者我要写书评

暂无评论

Keratocyte and fibroblast phenotypes in the repairing cornea

引用

PROGRESS IN RETINAL AND EYE RESEARCH 1999年第4期18卷 529-551页

作者： Fini, ME Tufts Univ Sch Med New England Med Ctr Vis Res LabsDept Ophthalmol Boston MA 02111 USA Tufts Univ Sch Med Dept Anat Boston MA 02111 USA Tufts Univ Sch Med Dept Cellular Biol Boston MA 02111 USA

In mammals, tissue damage is usually repaired by activation of a fibrotic response which saves the life of the organism, but which can never restore function to the damaged organ. In addition, fibrotic responses form the basis for diverse pathologies, including many that occur in the eye. it is intriguing, therefore, to observe the occasional circumstances in which repair in mammals appears to take on a regenerative character, such as during fetal wound healing or in certain types of corneal wounds. The thesis of this chapter is that the choice between regeneration or fibrosis lies in the control of fibroblast phenotype. The cornea of the eye has several features which make it a particularly useful model for the study of fibroblast phenotype. Studies discussed herein, identify failure to activate the transcription factor NF-kappa B as a control mechanism for inhibiting fibroblast activation in the cornea. Evidence is further presented for the view that transition in fibroblast phenotype in repair tissue is not simply a matter of differential gene expression, but is a developmental event which reflects changes in the hard wiring of signalling pathways by which the cell responds to environmental input. (C) 1999 Elsevier Science Ltd. Ali rights reserved.

关键词：细胞分化瘢痕/病理生理学角膜/细胞学角膜/损伤角膜/生理学细胞因子类/生理学成纤维细胞/分类成纤维细胞/细胞学成纤维细胞/生理学角蛋白细胞/分类角蛋白细胞/细胞学角蛋白细胞/生理学表型伤口愈合动物人类

来源：评论

学校读者我要写书评

暂无评论

Characterization of loricrin regulation in vitro and in transgenic mice

引用

DIFFERENTIATION 1999年第4期64卷 225-235页

作者： DiSepio, D Bickenbach, JR Longley, MA Bundman, DS Rothnagel, JA Roop, DR Baylor Coll Med Dept Cell Biol Houston TX 77030 USA Baylor Coll Med Dept Dermatol Houston TX 77030 USA

We have previously shown that the promoter of a 6.5 kb mouse loricrin clone contains a functional AP-I element and directs tissue-specific, but not differentiation-specific, expression. We now report the isolation of a 14-kb genomic clone containing an additional 7 kb of genomic sequence. The additional sequences limit expression of a reporter construct to differentiated keratinocytes in culture. The expression of the 6.5-kb and 14-kb loricrin constructs were also analyzed in transgenic mice. Significantly, loricrin was found in all layers of the epidermis of the 6.5-kb transgenics, including basal and spinous cells. The expression of the 14-kb clone was indistinguishable from that of the endogenous gene, confirming that the additional sequences contain negative regulatory elements that restrict loricrin expression to the granular layer in vivo. In addition, we show the AP-1 element localized in the loricrin proximal promoter is necessary but not sufficient for expression of the loricrin gene in vivo in transgenic mice. Finally, to gain further insight into how AP-1 family members regulate expression of the loricrin gene, we co-transfected the loricrin reporter constructs with expression plasmids for various fos and jun family members and demonstrated that c-Fos/Jun-B heterodimers could mimic the differentiation-specific induction of loricrin.

关键词：动物新生细胞分化细胞培养的氯霉素O-乙酰转移酶/遗传学克隆分子二聚作用基因表达调控基因报告基因组文库角蛋白细胞/细胞学角蛋白细胞/生理学膜蛋白质类/遗传学小鼠转基因诱变定点启动区(遗传学) 原癌基因蛋白质c-fos/代谢原癌基因蛋白质c-jun/代谢重组蛋白质类/生物合成调控序列核酸限制性内切酶图谱法皮肤/细胞学皮肤/代谢转录因子AP-1/代谢转染 β半乳糖苷酶类/遗传学动物小鼠

来源：评论

学校读者我要写书评

暂无评论

EGFR family-mediated signal transduction in the human keratinocyte cell line HaCaT

引用

EXPERIMENTAL CELL RESEARCH 1999年第2期252卷 432-438页

作者： Marqués, MM Martínez, N Rodríguez-García, I Alonso, A Deutsch Krebsforschungszentrum D-69120 Heidelberg Germany

We analyzed the formation of homo- and heterodimers between EGFR, ErbB2, and ErbB3 (members of the EGF receptor family) in the human skin keratinocyte cell Line HaCaT, in dependence of the added ligand. ErbB4 was not unambiguously identified. By immunoprecipitation and Western blots, we showed the formation of heterodimers between all members of the family. Whereas EGF and TGF-alpha strongly induced heterodimerization, no effect was observed with heregulin. At the concentrations used all ligands elicited a similar, differentiation-independent activation of erk1/2 MAP kinase, with the exception of heregulin which activated p42/44 only marginally. We also found that different ligands triggered different transcription patterns of "early genes," with the exception of heregulin which did not, modulate transcription. TGF-alpha was the most efficient Ligand in promoting incorporation of tritiated thymidine into the DNA. (C) 1999 Academic Press.

关键词：细胞系角蛋白细胞/生理学受体表皮生长因子/生理学受体 erbB-2/生理学受体 erbB-3/生理学信号传导人类

来源：评论

学校读者我要写书评

暂无评论

Caveolin-1 and-2 expression is differentially regulated in cultured keratinocytes and within the regenerating epidermis of cutaneous wounds

引用

EXPERIMENTAL CELL RESEARCH 2000年第1期258卷 23-32页

作者： Gassmann, MG Werner, S Max Planck Inst Biochem D-82152 Martinsried Germany ETH Honggerberg Inst Cell Biol CH-8093 Zurich Switzerland

Keratinocyte growth factor (KGF) and its receptor are involved in various types of epithelial repair processes. To gain insight into the molecular mechanisms of KGF action in the healing skin mound, we searched for genes which are regulated by this factor in cultured keratinocytes. Using the PCR-select technology we constructed a subtractive cDNA library. One of the KGF-regulated genes that we identified was shown to encode caveolin-1, a major component of caveolar membranes. Caveolin-1 is involved in a nide variety of cellular processes, particularly in the regulation of various signal transduction pathways. Caveolin-1 mRNA levels increased in cultured keratinocytes after KGF treatment. By in situ hybridization and immunohistochemistry we found a strong expression of caveolin-1 in the KGF-responsive basal keratinocytes of the epidermis and the hyperproliferative epithelium of the mound as well as in endothelial cells and in other cells of the granulation tissue. In 13-day wounds expression of caveolin-1 mRNA was restricted to the regenerated dermis, In addition to caveolin-1, the mRNA expression of caveolin-2, a second member of the caveolin family, was also induced in keratinocytes after stimulation with KGF but also with other growth factors and cytokines. In contrast to caveolin-1, caveolin-2 protein was expressed in all layers of the normal epidermis and in the suprabasal layers of the hyperproliferative wound epithelium. These results demonstrate a differential expression of caveolin-1 and -2 in proliferating versus differentiating keratinocytes. (C) 2000 Academic Press.

关键词：窖蛋白1 窖蛋白2 细胞质膜微囊蛋白细胞系表皮生长因子/药理学表皮/生理学表皮/病理生理学成纤维细胞生长因子10 成纤维细胞生长因子7 成纤维细胞生长因子荧光抗体技术间接基因表达调控/药物作用基因表达调控/生理学基因文库生长物质/药理学生长物质/生理学角蛋白细胞/生理学膜蛋白质类/分析膜蛋白质类/遗传学小鼠近交BALBC RNA 信使/遗传学皮肤/损伤转录遗传转化生长因子β/药理学肿瘤坏死因子α/药理学伤口愈合/药物作用伤口愈合/遗传学动物人类小鼠

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：