INCREASED MITOGENIC RESPONSE TO HEPARIN-BINDING EPIDERMAL GROWTH FACTOR-LIKE GROWTH-FACTOR IN VASCULAR SMOOTH-MUSCLE CELLS OF DIABETIC RATS

被引：19

作者：

FUKUDA, K ^{[1
]}

INUI, Y ^{[1
]}

KAWATA, S ^{[1
]}

HIGASHIYAMA, S ^{[1
]}

MATSUDA, Y ^{[1
]}

MAEDA, Y ^{[1
]}

IGURA, T ^{[1
]}

YOSHIDA, S ^{[1
]}

TANIGUCHI, N ^{[1
]}

MATSUZAWA, Y ^{[1
]}

机构：

[1] OSAKA UNIV,SCH MED,DEPT BIOCHEM,SUITA,OSAKA 565,JAPAN

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 1995年 / 15卷 / 10期

关键词：

HB-EGF; VASCULAR SMOOTH MUSCLE CELLS; HEPARAN SULFATE PROTEOGLYCAN; DIABETES MELLITUS;

D O I：

10.1161/01.ATV.15.10.1680

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

We investigated the mitogenic effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) in vascular smooth muscle cells (SMCs) obtained from rats with streptozotocin (STZ)-induced diabetes and evaluated the role of heparan sulfate proteoglycan (HSPG) in inducing these effects. HB-EGF significantly increased DNA synthesis in the SMCs of diabetic rats (STZ-SMCs) compared with control rats (control SMCs). However, the mitogenic effects of EGF, which shares EGF receptors with HB-EGF, and basic fibroblast growth factor, another heparin-binding growth factor, were similar in STZ-SMCs and control SMCs. The mitogenic response to HB-EGF in SMCs of insulin-treated diabetic rats was similar to the response in control SMCs. HB-EGF-induced autophosphorylation of ECF receptors was increased in STZ-SMCs compared with control SMCs, although the number of EGF receptors in STZ-SMCs was 40% of that in controls. This increased mitogenic response to HB-EGF in STZ-SMCs was completely inhibited by treatment with heparitinase, chlorate, and a synthetic peptide corresponding to the heparin-binding domain of HB-EGF. Compared with heparan sulfate isolated from control SMCs, heparan sulfate isolated from STZ-SMCs was of smaller molecular size and caused a greater mitogenic effect of HB-EGF. These findings suggest that the mitogenic response to HB-EGF is increased in SMCs of diabetic rats. Changes in cell-associated heparan sulfate in STZ-SMCs may be related to the increased mitogenic response to HB-EGF.

引用

页码：1680 / 1687

页数：8

共 45 条

[1] HEPARIN-BINDING EGF-LIKE GROWTH-FACTOR - CHARACTERIZATION OF RAT AND MOUSE CDNA CLONES, PROTEIN DOMAIN CONSERVATION ACROSS SPECIES, AND TRANSCRIPT EXPRESSION IN TISSUES [J].