Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts.
Preferential FGF18/FGFR activity in pseudoglandular versus canalicular stage human lung fibroblasts.
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DOI：
10.3389/fcell.2023.1220002
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发表时间：
2023
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
成纤维细胞生长因子（FGF）信号传导对于适当的肺分支形态发生、肺泡化和血管发育是必需的。FGF活性的失调与各种肺部疾病有关。最近，我们发现FGF 18通过调节间充质祖细胞促进人肺分支形态发生。然而，其潜在机制仍不清楚。因此，我们的目的是确定FGF 18及其受体（FGFR）在调节间充质细胞增殖，迁移和分化从假腺小管阶段的作用。我们进行siRNA测定以鉴定与FGF 18诱导的生物学过程相关的特异性FGFR。我们发现，FGF 18增加人胎肺成纤维细胞（HFLF）的增殖和迁移从这两个阶段。FGFR 2/FGFR 4在假腺期起重要作用。HFLF增殖，而FGFR 3/FGFR 4参与小管期。在假腺期和小管期，FGF 18分别通过FGFR 2和FGFR 4促进HFLF迁移。最后，我们提供的证据表明，FGF 18治疗导致肌成纤维细胞标志物（ACTA 2和COL 1A 1）的表达减少，脂肪成纤维细胞标志物（ADRP和PPARγ）的表达增加，在两个阶段HFLF。然而，参与该过程的特定FGF 18/FGFR复合物根据阶段而变化。我们的研究结果表明，在人肺发育的背景下，FGF 18往往与不同的FGFRs相关联，以启动间充质细胞的特定生物学过程。
Fibroblast growth factor (FGF) signaling is necessary for proper lung branching morphogenesis, alveolarization, and vascular development. Dysregulation of FGF activity has been implicated in various lung diseases. Recently, we showed that FGF18 promotes human lung branching morphogenesis by regulating mesenchymal progenitor cells. However, the underlying mechanisms remain unclear. Thus, we aimed to determine the role of FGF18 and its receptors (FGFR) in regulating mesenchymal cell proliferation, migration, and differentiation from pseudoglandular to canalicular stage. We performed siRNA assays to identify the specific FGFR(s) associated with FGF18-induced biological processes. We found that FGF18 increased proliferation and migration in human fetal lung fibroblasts (HFLF) from both stages. FGFR2/FGFR4 played a significant role in pseudoglandular stage. HFLF proliferation, while FGFR3/FGFR4 were involved in canalicular stage. FGF18 enhanced HFLF migration through FGFR2 and FGFR4 in pseudoglandular and canalicular stage, respectively. Finally, we provide evidence that FGF18 treatment leads to reduced expression of myofibroblast markers (ACTA2 and COL1A1) and increased expression of lipofibroblast markers (ADRP and PPARγ) in both stages HFLF. However, the specific FGF18/FGFR complex involved in this process varies depending on the stage. Our findings suggest that in context of human lung development, FGF18 tends to associate with distinct FGFRs to initiate specific biological processes on mesenchymal cells.
影响因子：
5.7
作者：
Li P;Zhang L;Yu X;Tong R;Di X;Mao Y;Gao Y;Zhang K;Feng L;Cheng S
通讯作者：
Cheng S