The stromal cell-derived factor-1alpha/CXCR4 ligand-receptor axis is critical for progenitor survival and migration in the pancreas.

The stromal cell-derived factor-1alpha/CXCR4 ligand-receptor axis is critical for progenitor survival and migration in the pancreas.
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DOI:
10.1083/jcb.200304153
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发表时间:
2003-11-24
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Sarvetnick N
Sarvetnick N
中科院分区:
其他
文献类型:
--
作者:
Kayali AG;Van Gunst K;Campbell IL;Stotland A;Kritzik M;Liu G;Flodström-Tullberg M;Zhang YQ;Sarvetnick N

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在个体发育过程中,SDF-1α/CXCR4配体/趋化因子受体对是形成适当图案所必需的,并刺激关键细胞类型的生长和分化。在这里,我们证明了SDF-1α和CXCR4在胎儿胰腺中的表达。我们发现α及其受体CXCR4表达于胰岛,CXCR4表达于干扰素γ非肥胖型糖尿病小鼠再生胰腺的增殖管上皮及其周围。我们发现SDF-1α能刺激胰管细胞中Akt、丝裂原活化蛋白激酶和Src的磷酸化。此外,迁移分析表明,SDF-1α对导管细胞迁移有刺激作用。重要的是,阻断干扰素α-非肥胖糖尿病小鼠的SDF-1γ/CXCR4轴导致胰腺导管细胞增殖减少和凋亡增加。综上所述,这些数据表明,SDF-1α-CXCR4配体受体轴在维持胰腺再生过程中导管细胞的存活、增殖和迁移过程中是必不可少的组成部分。
The SDF-1α/CXCR4 ligand/chemokine receptor pair is required for appropriate patterning during ontogeny and stimulates the growth and differentiation of critical cell types. Here, we demonstrate SDF-1α and CXCR4 expression in fetal pancreas. We have found that SDF-1α and its receptor CXCR4 are expressed in islets, also CXCR4 is expressed in and around the proliferating duct epithelium of the regenerating pancreas of the interferon (IFN) γ–nonobese diabetic mouse. We show that SDF-1α stimulates the phosphorylation of Akt, mitogen-activated protein kinase, and Src in pancreatic duct cells. Furthermore, migration assays indicate a stimulatory effect of SDF-1α on ductal cell migration. Importantly, blocking the SDF-1α/CXCR4 axis in IFNγ-nonobese diabetic mice resulted in diminished proliferation and increased apoptosis in the pancreatic ductal cells. Together, these data indicate that the SDF-1α–CXCR4 ligand receptor axis is an obligatory component in the maintenance of duct cell survival, proliferation, and migration during pancreatic regeneration.
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