Hepatocyte Growth Factor Regulates Human Trophoblast Motility and Invasion: a Role for Nitric Oxide

Overview

Journal Br J Pharmacol

Publisher Wiley

Specialty Pharmacology

Date 1999 Sep 28

PMID 10498850

Citations 38

Authors

J E Cartwright

D P Holden

G S Whitley

Affiliations

Soon will be listed here.

Abstract

1. The expression of hepatocyte growth factor (HGF) is essential for normal placental development although its function is unknown. In this study we examined the effect of HGF on trophoblast cell motility and invasion of fibrin gels and investigated the possible role of nitric oxide (NO) in this process. 2. The human extravillous trophoblast cell line SGHPL-4 express both the constitutive and inducible isoforms of nitric oxide synthase (NOS). 3. HGF significantly stimulates cell motility in monolayer culture, the invasion of fibrin gels and the production of guanosine 3':5'-cyclic monophosphate (cyclic GMP). 4. Invasion, motility and cyclic GMP production were inhibited by Ng-monomethyl-L-arginine (L-NMMA). 5. Cell motility was also significantly inhibited by the inducible NOS specific inhibitor 1400 W. 6. Neither 8 Br-cyclic GMP nor the NO donor spermine-NO had any significant effect on basal trophoblast cell motility. 7. The data presented in this study demonstrate a direct effect of trophoblast-derived NO synthesis on trophoblast cell function and support the idea that HGF is involved in the regulation of trophoblast invasion through mechanisms that involve the production of NO. However neither exogenous NO nor activation of cyclic GMP-dependent pathways alone are sufficient to stimulate trophoblast cell motility.

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