KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts
KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts
复制标题
DOI：
10.1016/j.bbrc.2005.10.144
复制
发表时间：
2005-12-30
影响因子：
3.1
通讯作者：
Kohno, N
中科院分区：
文献类型：
--
作者：
Ohshimo, S;Yokoyama, A;Kohno, N
KL-6（一种 MUC1 粘蛋白）的血清水平是临床上对各种间质性肺疾病有用的标志物。先前的研究表明，KL-6 可促进人成纤维细胞的趋化性。然而，KL-6 的病理生理学作用仍然知之甚少。在这里，我们进一步研究了 KL-6 在肺成纤维细胞增殖和凋亡中的功能。 KL-6 加速了所有受检人肺成纤维细胞的增殖并抑制其凋亡。抗 KL-6 单克隆抗体可以抵消 KL-6 对人肺成纤维细胞诱导的这两种作用。 KL-6 的促纤维增殖和抗细胞凋亡作用大于最大有效浓度的血小板源性生长因子、碱性成纤维细胞生长因子和转化生长因子-β 的作用并与之相加。这些发现表明，上皮衬里液中 KL-6 水平的增加可能会刺激间质性肺疾病的纤维化过程，并提高应用抗 KL-6 抗体治疗间质性肺疾病的可能性。 (c) 2005 Elsevier Inc. 保留所有权利。
The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-beta. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases. (c) 2005 Elsevier Inc. All rights reserved.