Involvement of heparin-binding EGF-like growth factor and its processing by metalloproteinases in early epithelial morphogenesis of the submandibular gland.
Involvement of heparin-binding EGF-like growth factor and its processing by metalloproteinases in early epithelial morphogenesis of the submandibular gland.
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肝素结合 EGF 样生长因子及其金属蛋白酶加工参与下颌下腺早期上皮形态发生。
DOI：
10.1006/dbio.2001.0351
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发表时间：
2001
影响因子：
2.7
通讯作者：
Y. Hieda
中科院分区：
文献类型：
--
作者：
Yuko Umeda;Yuji Miyazaki;H. Shiinoki;Shigeki Higashiyama;Yasuo Nakanishi;Y. Hieda
本研究以发育中的小鼠下颌下腺(SMG)为模型，研究了表皮生长因子(EGF)家族的一员--肝素结合型EGF样生长因子(HB-EGF)在器官发育中的作用。RT-PCR检测到HB-EGF mRNA在发育中的SMG中表达，主要表达于胚胎SMG的上皮细胞，间质中有少量表达。与HB-EGF的肝素结合区对应的合成肽和抗HB-EGF中和抗体可抑制上皮细胞的形态发生。使用EGF受体配体依赖的细胞系EP170.7进行体外实验，我们可以检测到SMG条件培养液中的生长因子活性，这种活性被抗HB-EGF抗体显著降低。此外，羟胺酸金属蛋白酶抑制剂OSU8-1可抑制包括HB-EGF在内的EGFR配体的加工，显著降低条件培养液中生长因子的活性，几乎完全抑制SMG的形态发生。加入可溶性HB-EGF可部分逆转其对形态发生的抑制作用。我们的结果首次证明HB-EGF是器官发育过程中上皮形态发生的重要调节因子，突出了金属蛋白酶对其加工的重要性。
In the present study, the role of a member of the epidermal growth factor (EGF) family, heparin-binding EGF-like growth factor (HB-EGF), in organ development was investigated by using developing mouse submandibular gland (SMG), in which the EGF receptor signaling and heparan sulfate chains have been implicated. HB-EGF mRNA was detected in developing SMG by RT-PCR analysis and was expressed mainly in epithelium and weakly in mesenchyme of the embryonic SMG. Epithelial morphogenesis was inhibited by a synthetic peptide corresponding to the heparin-binding domain of HB-EGF and by anti-HB-EGF neutralizing antibody. An in vitro assay using an EGF receptor ligand-dependent cell line, EP170.7 cells, allowed us to detect the growth factor activity in SMG-conditioned media, which was significantly reduced by anti-HB-EGF antibody. Furthermore, treatment of SMG rudiments with the hydroxamate-based metalloproteinase inhibitor OSU8-1, which inhibits processing of EGFR ligands including HB-EGF, markedly diminished the growth factor activity in conditioned media and resulted in almost complete inhibition of SMG morphogenesis. The inhibitory effects on morphogenesis were reversed, though partially, by adding the soluble form of HB-EGF. Our results provide the first evidence that HB-EGF is a crucial regulator of epithelial morphogenesis during organ development, highlighting the importance of its processing by metalloproteinases.
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影响因子：
2.7
作者：
Kashimata, M;Sayeed, S;Gresik, EW
通讯作者：
Gresik, EW
DOI：
10.1006/bbrc.1993.1020
发表时间：
1993-01-15
影响因子：
3.1
作者：
ABRAHAM, JA;DAMM, D;EZEKOWITZ, RAB
通讯作者：
EZEKOWITZ, RAB
影响因子：
4.6
作者：
Lucia Schuger;Gibbes R. Johnson;Kevin Gilbride;Gregory D. Plowman;Richard Mandel
通讯作者：
Lucia Schuger;Gibbes R. Johnson;Kevin Gilbride;Gregory D. Plowman;Richard Mandel
影响因子：
--
作者：
S. Das;I. Chakraborty;B. Paria;Xiaohong Wang;G. Plowman;S. Dey
通讯作者：
S. Das;I. Chakraborty;B. Paria;Xiaohong Wang;G. Plowman;S. Dey
影响因子：
56.9
作者：
Peschon, JJ;Slack, JL;Black, RA
通讯作者：
Black, RA