Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner
Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner
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DOI：
10.1152/ajpcell.00617.2008
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发表时间：
2009-04-01
影响因子：
5.5
通讯作者：
Sorisky, Alexander
中科院分区：
文献类型：
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作者：
Molgat, Andre S. D.;Gagnon, AnneMarie;Sorisky, Alexander
Molgat AS, Gagnon A, Sorisky A.巨噬细胞条件培养基以pdgf依赖的方式阻止前脂肪细胞凋亡。[J] .中国生物医学工程学报，2009,31(6):757- 765。2009年2月18日首次出版；doi: 10.1152 / ajpcell.00617.2008。肥胖与巨噬细胞积聚和脂肪组织炎症有关。据报道，巨噬细胞分泌因子抑制前脂肪细胞向脂肪细胞的分化，并调节成脂细胞外基质基因的表达。为了扩大我们对巨噬细胞及其与前脂肪细胞相互作用范围的理解，我们研究了巨噬细胞对前脂肪细胞存活的影响。3T3-L1前脂肪细胞急性暴露于J774A.1巨噬细胞条件培养基（MacCM）可刺激血小板衍生生长因子受体（PDGFR）酪氨酸磷酸化4.1倍。PDGFR下游靶点Akt和ERK1/2的磷酸化含量被PDGF免疫中和或选择性PDGFR抑制剂伊马替尼抑制后显著增加（分别为5.3倍和2.4倍）。无血清J774A.1-MacCM或RAW264.7-MacCM完全阻止血清剥夺正常诱导的3T3-L1前脂肪细胞凋亡。在无血清对照培养基中单独添加PDGF足以阻止3T3-L1前脂肪细胞凋亡。通过添加伊马替尼或PDGF免疫缺失MacCM抑制PDGFR激活，有效地破坏了促生存作用。总之，我们的数据表明，MacCM以pdgf依赖的方式促进前脂肪细胞的存活。
Molgat AS, Gagnon A, Sorisky A. Preadipocyte apoptosis is prevented by macrophage-conditioned medium in a PDGF-dependent manner. Am J Physiol Cell Physiol 296: C757-C765, 2009. First published February 18, 2009; doi:10.1152/ajpcell.00617.2008.-Obesity is associated with macrophage accumulation and inflammation in adipose tissue. Macrophage-secreted factors have been reported to inhibit the differentiation of preadipocytes into adipocytes and to modulate adipogenic extracellular matrix gene expression. To enlarge our understanding of macrophages and the scope of their interactions with preadipocytes, we investigated their effect on preadipocyte survival. Acute exposure of 3T3-L1 preadipocytes to J774A.1 macrophage-conditioned medium (MacCM) stimulated platelet-derived growth factor receptor (PDGFR) tyrosine phosphorylation by 4.1-fold. There were significant increases in the phosphocontent of downstream PDGFR targets Akt and ERK1/2 (5.3-fold and 2.4-fold, respectively) that were inhibited by PDGF immunoneutralization or by the selective PDGFR inhibitor imatinib. Serum-free J774A.1-MacCM or RAW264.7-MacCM completely prevented 3T3-L1 preadipocyte apoptosis normally induced by serum deprivation. Addition of PDGF alone to serum-free control medium was sufficient to prevent 3T3-L1 preadipocyte apoptosis. Inhibition of PDGFR activation by MacCM, either by addition of imatinib or by PDGF immunodepletion of MacCM, effectively disrupted the prosurvival effect. In summary, our data indicate that MacCM promotes preadipocyte survival in a PDGF-dependent manner.