Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis.
Neuropilin 1 Mediates Keratinocyte Growth Factor Signaling in Adipose-Derived Stem Cells: Potential Involvement in Adipogenesis.
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DOI：
10.1155/2018/1075156
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发表时间：
2018
影响因子：
4.3
通讯作者：
Marchese C
中科院分区：
文献类型：
--
作者：
Ceccarelli S;Nodale C;Vescarelli E;Pontecorvi P;Manganelli V;Casella G;Onesti MG;Sorice M;Romano F;Angeloni A;Marchese C
脂肪生成受到复杂的分子网络的调节，包括成纤维细胞生长因子。先前报道角质形成细胞生长因子（KGF）可促进大鼠前脂肪细胞的增殖，尽管其特异性受体 FGFR2-IIIb/KGFR 的表达实际上并未在间充质细胞中检测到。在这里，我们证明人类脂肪干细胞（ASC）在脂肪形成分化过程中表现出 KGF 表达增加，特别是在早期步骤。此外，KGF 能够诱导这些细胞中 ERK 和 p38 MAPK 通路的瞬时激活。此外，KGF 促进 ASC 分化并支持分化途径的激活，例如 PI3K/Akt 和视网膜母细胞瘤蛋白 (Rb) 的激活。值得注意的是，我们在 ASC 中仅观察到少量的 FGFR2-IIIb，这似乎与 KGF 活性无关。在这里，我们首次证明 Neuropilin 1 (NRP1) 是一种在 ASC 中表达的跨膜糖蛋白，作为某些生长因子的辅助受体，负责这些细胞中 KGF 依赖性途径的激活。我们的研究有助于阐明人类脂肪生成的分子基础，证明 KGF 在此过程的早期步骤中的作用，并指出 NRP1 作为 ASC 中 KGF 作用的先前未知介质的作用。
Adipogenesis is regulated by a complex network of molecules, including fibroblast growth factors. Keratinocyte growth factor (KGF) has been previously reported to promote proliferation on rat preadipocytes, although the expression of its specific receptor, FGFR2-IIIb/KGFR, is not actually detected in mesenchymal cells. Here, we demonstrate that human adipose-derived stem cells (ASCs) show increased expression of KGF during adipogenic differentiation, especially in the early steps. Moreover, KGF is able to induce transient activation of ERK and p38 MAPK pathways in these cells. Furthermore, KGF promotes ASC differentiation and supports the activation of differentiation pathways, such as those of PI3K/Akt and the retinoblastoma protein (Rb). Notably, we observed only a low amount of FGFR2-IIIb in ASCs, which seems not to be responsible for KGF activity. Here, we demonstrate for the first time that Neuropilin 1 (NRP1), a transmembrane glycoprotein expressed in ASCs acting as a coreceptor for some growth factors, is responsible for KGF-dependent pathway activation in these cells. Our study contributes to clarify the molecular bases of human adipogenesis, demonstrating a role of KGF in the early steps of this process, and points out a role of NRP1 as a previously unknown mediator of KGF action in ASCs.
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影响因子：
3.5
作者：
Bhattacharya, Indranil;Ullrich, Axel
通讯作者：
Ullrich, Axel
影响因子：
4.9
作者：
Gerhard, G. S.;Styer, A. M.;Strodel, W. E.;Roesch, S. L.;Yavorek, A.;Carey, D. J.;Wood, G. C.;Petrick, A. T.;Gabrielsen, J.;Ibele, A.;Benotti, P.;Rolston, D. D.;Still, C. D.;Argyropoulos, G.
通讯作者：
Argyropoulos, G.
影响因子：
5.3
作者：
Ceccarelli S;D'Amici S;Vescarelli E;Coluccio P;Matricardi P;di Gioia C;Benedetti Panici P;Romano F;Frati L;Angeloni A;Marchese C
通讯作者：
Marchese C
影响因子：
3.7
作者：
Kim S;Ahn C;Bong N;Choe S;Lee DK
通讯作者：
Lee DK
DOI：
10.1073/pnas.190343597
发表时间：
2000-09-26
影响因子：
11.1
作者：
Classon, M;Kennedy, BK;Harlow, E
通讯作者：
Harlow, E