HEPARIN-BINDING GROWTH-FACTOR TYPE-1 (ACIDIC FIBROBLAST GROWTH-FACTOR) - A POTENTIAL BIPHASIC AUTOCRINE AND PARACRINE REGULATOR OF HEPATOCYTE REGENERATION
HEPARIN-BINDING GROWTH-FACTOR TYPE-1 (ACIDIC FIBROBLAST GROWTH-FACTOR) - A POTENTIAL BIPHASIC AUTOCRINE AND PARACRINE REGULATOR OF HEPATOCYTE REGENERATION
复制标题
DOI：
10.1073/pnas.86.19.7432
复制
发表时间：
1989-10-01
影响因子：
11.1
通讯作者：
MCKEEHAN, WL
中科院分区：
文献类型：
--
作者：
KAN, M;HUANG, JS;MCKEEHAN, WL
肝素结合生长因子1型（HBGF-1，有时称为酸性成纤维细胞生长因子）是肝脏再生的潜在重要因素。单独的HBGF-1 （60 pM时的一半最大效应）刺激肝细胞DNA合成并结合到一个高亲和力受体（Kd = 62 pM；每个细胞5000）。表皮生长因子（EGF）中和或掩盖HBGF-1的有丝分裂作用，同时出现低亲和力HBGF-1结合位点。HBGF-1降低了β型转化生长因子的抑制作用。（TGF-. β）对EGF刺激的影响。纳摩尔水平的HBGF-1降低了EGF刺激。部分肝切除术后，肝脏HBGF-1基因表达的增加先于EGF同源物TGF- α表达的增加。和非实质细胞来源的TGF- β。在再生的肝脏中。HBGF-1 mRNA在肝细胞和非实质细胞中均有表达，并在部分肝切除术后肝组织中持续表达7天。HBGF-1通过高亲和力受体作用，是早期自分泌刺激的候选物，在EGF/TGF- α之前或同时驱动肝细胞DNA合成。刺激。它可能允许肝细胞在低水平TGF- β存在的情况下增殖。一个EGF / TGF -.alpha。-依赖性改变HBGF-1受体表型，增加非实质细胞来源的HBGF-1和TGF- β水平。可能有助于限制肝细胞增殖。
Heparin-binding growth factor type 1 (HBGF-1; sometimes termed acidic fibroblast growth factor) is potentially an important factor in liver regeneration. HBGF-1 alone (half-maximal effect at 60 pM) stimulated hepatocyte DNA synthesis and bound to a high-affinity receptor (Kd = 62 pM; 5000 per cell). Epidermal growth factor (EGF) neutralized or masked the mitogenic effect of HBGF-1 concurrent with appearance of low-affinity HBGF-1 binding sites. HBGF-1 reduced the inhibitory effect of transforming growth factor type .beta. (TGF-.beta.) on the EGF stimulus. Nanomolar levels of HBGF-1 decreased the EGF stimulus. An increase in hepatic HBGF-1 gene expression after partial hepatectomy precedes increases in expression of the EGF homolog, TGF-.alpha., and nonparenchymal-cell-derived TGF-.beta. in the regenerating liver. Expression of HBGF-1 mRNA occurs in both hepatocytes and nonparenchymal cells and persists for 7 days in liver tissue after partial hepatectomy. HBGF-1 acting through a high-affinity receptor is a candidate for the early autocrine stimulus that drives hepatocyte DNA synthesis prior to or concurrent with the EGF/TGF-.alpha. stimulus. It may allow hepatocyte proliferation to proceed in the presence of low levels of TGF-.beta.. An EGF/TGF-.alpha.-dependent change in HBGF-1 receptor phenotype and increasing levels of nonparenchymal-cell-derived HBGF-1 and TGF-.beta. may serve to limit hepatocyte proliferation.