Masamune Atsushi, Satoh Masahiro, Kikuta Kazuhiro, Suzuki Noriaki, Shimosegawa Tooru
Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cyo, Aoba-ku, Sendai 980-8574, Japan.
World J Gastroenterol. 2005 Jun 14;11(22):3385-91. doi: 10.3748/wjg.v11.i22.3385.
To clarify the role of Janus kinase-signal transducers and activators of transcription (JAK-STAT) pathway in platelet-derived growth factor (PDGF) induced proliferation in activated pancreatic stellate cells (PSCs).
PSCs were isolated from rat pancreas tissue, and used in their culture-activated, myofibroblast-like phenotype. STAT-specific binding activity was assessed by electrophoretic mobility shift assay. Activation of Src, JAK2, STAT1, STAT3, and ERK was determined by Western blotting using anti-phospho-specific antibodies. Cell proliferation was assessed by measuring the incorporation of 5-bromo-2'-deoxyuridine.
PDGF-BB induced STAT-specific binding activity, and activation of Src, JAK2, STAT1, STAT3, and ERK. Ethanol and acetaldehyde at clinically relevant concentrations decreased basal activation of JAK2 and STAT3. PDGF-induced activation of STAT1 and STAT3 was inhibited by a Src inhibitor PP1 and a JAK2 inhibitor AG490, whereas PDGF-induced activation of ERK was inhibited by PP1, and not by AG490. PDGF-induced proliferation was inhibited by PP1 and AG490 as well as by STAT3 antisense oligonucleotide.
PDGF-BB activated JAK2-STAT pathway via Src-dependent mechanism. Activation of JAK2-STAT3 pathway, in addition to ERK, may play a role in PDGF-induced proliferation of PSCs.
阐明 Janus 激酶-信号转导子和转录激活子（JAK-STAT）通路在血小板衍生生长因子（PDGF）诱导活化胰腺星状细胞（PSC）增殖中的作用。
从大鼠胰腺组织中分离出 PSC，并将其培养成活化的、肌成纤维细胞样表型。通过电泳迁移率变动分析评估 STAT 特异性结合活性。使用抗磷酸化特异性抗体通过蛋白质印迹法测定 Src、JAK2、STAT1、STAT3 和 ERK 的激活情况。通过测量 5-溴-2'-脱氧尿苷的掺入来评估细胞增殖。
PDGF-BB 诱导 STAT 特异性结合活性以及 Src、JAK2、STAT1、STAT3 和 ERK 的激活。临床相关浓度的乙醇和乙醛降低了 JAK2 和 STAT3 的基础激活。Src 抑制剂 PP1 和 JAK2 抑制剂 AG490 抑制了 PDGF 诱导的 STAT1 和 STAT3 的激活，而 PDGF 诱导的 ERK 的激活被 PP1 抑制，而不被 AG490 抑制。PP1、AG490 以及 STAT3 反义寡核苷酸抑制了 PDGF 诱导的增殖。
PDGF-BB 通过 Src 依赖性机制激活 JAK2-STAT 通路。JAK2-STAT3 通路的激活，除了 ERK 外，可能在 PDGF 诱导的 PSC 增殖中起作用。
