Department of Biological Sciences, Sookmyung Women's University, Seoul, Republic of Korea; Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
Department of Biology, Chungnam National University, Daejeon, Republic of Korea.
Biochem Biophys Res Commun. 2014 Apr 18;446(4):1237-42. doi: 10.1016/j.bbrc.2014.03.099. Epub 2014 Mar 28.
Loss-of-function mutations in angiopoietin-like 3 (ANGPTL3) cause familial hypobetalipoproteinemia type 2 (FHBL2) in humans. ANGPTL3 belongs to the angiopoietin-like family, the vascular endothelial growth factor family that is structurally similar to angiopoietins and is known for a regulator of lipid and glucose metabolism, although it is unclear how mutations in ANGPTL3 lead to defect in liver development in the vertebrates. We report here that angptl3 is primarily expressed in the zebrafish developing liver and that morpholino (MO) knockdown of Angptl3 reduces the size of the developing liver, which is caused by suppression of cell proliferation, but not by enhancement of apoptosis. However, MO knockdown of Angptl3 did not alter angiogenesis in the developing liver. Additionally, disruption of zebrafish Angptl3 elicits the hypocholesterolemia phenotype that is characteristic of FHBL2 in humans. Together, our findings propose a novel role for Angptl3 in liver cell proliferation and maintenance during zebrafish embryogenesis. Finally, angptl3 morphants will serve as a good model for understanding the pathophysiology of FHBL2.
血管生成素样蛋白 3（ANGPTL3）的功能丧失突变会导致人类家族性低β脂蛋白血症 2 型（FHBL2）。ANGPTL3 属于血管生成素样家族，与血管生成素结构相似，是血管内皮生长因子家族的一员，已知其是脂质和葡萄糖代谢的调节剂，尽管尚不清楚 ANGPTL3 突变如何导致脊椎动物肝脏发育缺陷。我们在这里报告，angptl3 在斑马鱼发育中的肝脏中主要表达，而 Angptl3 的 morpholino（MO）敲低会减少发育中的肝脏的大小，这是由细胞增殖的抑制引起的，而不是由细胞凋亡的增强引起的。然而，Angptl3 的 MO 敲低并没有改变发育中的肝脏的血管生成。此外，破坏斑马鱼 Angptl3 会引发 FHBL2 患者所特有的低胆固醇血症表型。总之，我们的研究结果提出了 Angptl3 在斑马鱼胚胎发生过程中肝脏细胞增殖和维持中的新作用。最后，angptl3 morphants 将作为理解 FHBL2 病理生理学的良好模型。
