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Calcitonin gene-related peptide increases proliferation of human HaCaT keratinocytes by activation of MAP kinases.

机译:降钙素基因相关肽通过激活MAP激酶来增加人HaCaT角质形成细胞的增殖。

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摘要

Psoriasis is a chronic disease characterized by keratinocyte hyperproliferation and inflammation. It has been demonstrated that the expression of calcitonin gene-related peptide (CGRP) is elevated in psoriasis lesions and CGRP-containing neuropeptide nerve fibers are denser in the psoriatic epidermis. CGRP has been previously described to influence proliferation of several cell types, such as Schwann cell, tracheal epithelial cells, and human gingival fibroblasts. In the present study, we determined the effect of CGRP on HaCaT keratinocyte proliferation and the role of mitogen-activated protein kinases (MAPKs) in CGRP induced keratinocyte proliferation. Our data indicate CGRP increased [(3)H]-thymidine incorporation and MTT activity of HaCaT in a concentration-dependent manner. CGRP also enhanced serum-induced HaCaT cell proliferation. HaCaT cells cultured with CGRP had a significant increase in phosphorylated ERK1/2, p38 and JNK, and CGRP induced DNA synthesis was inhibited by PD 98059 or SB 203580, selective inhibitors of MAP kinase kinase (MEK, which is upstream from ERK) and p38, respectively. These findings suggest that HaCaT cell proliferate in response to CGRP, which is mediated by phosphorylation of ERK1/2 and p38 MAPK.
机译:银屑病是一种以角质形成细胞过度增殖和发炎为特征的慢性疾病。已经证明,在牛皮癣病灶中降钙素基因相关肽(CGRP)的表达升高,并且在牛皮癣表皮中含CGRP的神经肽神经纤维密度更高。先前已经描述了CGRP影响几种细胞类型的增殖,例如雪旺氏细胞,气管上皮细胞和人牙龈成纤维细胞。在本研究中,我们确定了CGRP对HaCaT角质形成细胞增殖的影响以及有丝分裂原激活的蛋白激酶(MAPK)在CGRP诱导的角质形成细胞增殖中的作用。我们的数据表明,CGRP以浓度依赖的方式增加了HaCaT的[(3)H]-胸苷掺入和MTT活性。 CGRP还增强了血清诱导的HaCaT细胞增殖。用CGRP培养的HaCaT细胞的磷酸化ERK1 / 2,p38和JNK显着增加,并且CGRP诱导的DNA合成被PD 98059或SB 203580(MAP激酶激酶(MEK,位于ERK的上游)和p38的选择性抑制剂)抑制, 分别。这些发现表明,HaCaT细胞在响应CGRP时增殖,这是由ERK1 / 2和p38 MAPK的磷酸化介导的。

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