肌成纤维细胞
自分泌信号
细胞生物学
Wnt信号通路
降钙素基因相关肽
旁分泌信号
化学
SMAD公司
细胞外基质
内科学
内分泌学
转化生长因子
信号转导
纤维化
生物
医学
受体
生物化学
神经肽
作者
Özgecan Kayalar,Füsun Öztay
摘要
There are contradictory views on which calcitonin gene-related peptide (CGRP) causes pulmonary fibrosis. Fibrotic potency of CGRP was tested and compared to that of transforming growth factor-β (TGF-β). Myofibroblast differentiation, cell proliferation, and activations of TGF-β and Wnt pathways were examined for 24, 48, and 72 h in A549 and MRC5 cell lines stimulated with CGRP and TGF-β. CGRP-induced cell proliferation in MRC5s early on while cell proliferation in A549 occurred progressively. CGRP promoted fibroblast-myofibroblast differentiation by inducing the transcription of ACTA2, COL1A1, SMAD2/3, and SMAD4 genes, the production of collagen, fibronectin, α-smooth muscle actin, and activation of TGF-β signaling starting from 24 h. Additionally, TGF-β signaling induced by CGRP decreased the DKK1 level and activated the Wnt signaling in MRC5s. After CGRP stimulation, Wnt7a levels were increased from 24 to 72 h, while Wnt5a levels were elevated at 72 h in MRC5s. CGRP did not induce epithelial-mesenchymal transition in A549s, unlike TGF-β. A comparison of fibrotic potency of CGRP and TGF-β showed that TGF-β is a powerful profibrotic molecule and induces earlier myofibroblast differentiation. Even so, CGRP promotes myofibroblast differentiation and extracellular matrix production by inducing Smad-dependent-TGF-β and Wnt signalings via autocrine and paracrine signalings in MRC5s.
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