Thrombospondin-1 expression may be implicated in liver atrophic mechanism due to obstructed portal venous flow.
Thrombospondin-1 expression may be implicated in liver atrophic mechanism due to obstructed portal venous flow.
复制标题
Thrombospondin-1 表达可能与门静脉血流阻塞导致的肝脏萎缩机制有关。
作者：
Hayashi H;Kuroki H;Higashi T;Takeyama H;Yokoyama N;Okabe H;Nitta H;Beppu T;Takamori H;Baba H.
AimLiver是一个惊人的器官，可以根据血流条件反向进行再生和萎缩变化。虽然再生机制已被广泛研究，萎缩的机制仍有待澄清。方法和结果为了评估肝萎缩的分子机制，由于门静脉血流量减少，我们分析了萎缩和肥厚的肝门静脉栓塞诱导的基因表达在三个人的肝组织中使用微阵列分析。血小板反应蛋白（TSP）-1是一种细胞外蛋白，通过激活转化生长因子-β/Smad信号通路，参与肝再生的负调控，在人门静脉血流阻塞导致的萎缩性肝组织中表达上调最多。通过HE和增殖细胞核抗原染色和末端脱氧核苷酸转移酶介导的地高辛-dUTP缺口末端标记证实肝脏萎缩和肥大变化。在门静脉结扎的动物体内模型中，TSP-1和磷酸化Smad 2的表达在6 h及之后在门静脉结扎的肝脏中持续诱导，而在门静脉未结扎的肝脏中，诱导在6 h是短暂的。事实上，虽然在48 h的增殖细胞核抗原表达代表的细胞增殖诱导在门静脉结扎的肝脏，窦扩张和肝细胞死亡与末端脱氧核苷酸转移酶介导的地高辛-dUTP缺口末端标记检测在48 h的门静脉结扎liver.Conclusionsobstructed门静脉血流诱导持续TSP-1表达和转化生长因子-β/Smad信号激活在萎缩的肝脏。凝血酶敏感蛋白-1可能作为促萎缩因素参与了门静脉血流阻塞导致的肝脏萎缩性变化。
AimLiver is an amazing organ that can undergo regenerative and atrophic changes inversely, depending on blood flow conditions. Although the regenerative mechanism has been extensively studied, the atrophic mechanism remains to be elucidated.Methods and ResultsTo assess the molecular mechanism of liver atrophy due to reduced portal blood flow, we analyzed the gene expressions between atrophic and hypertrophic livers induced by portal vein embolization in three human liver tissues using microarray analyses. Thrombospondin (TSP)‐1is an extracellular protein and a negative regulator of liver regeneration through its activation of the transforming growth factor‐β/Smad signaling pathway.TSP‐1was extracted as the most upregulated gene in atrophic liver compared to hypertrophic liver due to portal flow obstruction in human. Liver atrophic and hypertrophic changes were confirmed by HE and proliferating cell nuclear antigen staining and terminal deoxynucleotidyl transferase‐mediated digoxigenin‐dUTP nick‐end labeling. In anin vivomodel with portal ligation,TSP‐1and phosphorylated Smad2 expression were continuously induced at 6 h and thereafter in the portal ligated liver, whereas the induction was transient at 6 h in the portal non‐ligated liver. Indeed, while cell proliferation represented by proliferating cell nuclear antigen expression at 48 h was induced in the portal ligated liver, the sinusoidal dilatation and hepatocyte cell death with terminal deoxynucleotidyl transferase‐mediated digoxigenin‐dUTP nick‐end labeling was detectable at 48 h in the portal ligated liver.ConclusionsObstructed portal flow induces persistentTSP‐1expression and transforming growth factor‐β/Smad signal activation in atrophic liver. Thrombospondin‐1 may be implicated in the liver atrophic change due to obstructed portal flow as a pro‐atrophic factor.