Effect of endothelin-1 (1-31) on human mesangial cell proliferation

Citation
M. Yoshizumi et al., Effect of endothelin-1 (1-31) on human mesangial cell proliferation, JPN J PHARM, 84(2), 2000, pp. 146-155
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JAPANESE JOURNAL OF PHARMACOLOGY
ISSN journal
0021-5198 → ACNP
Volume
84
Issue
2
Year of publication
2000
Pages
146 - 155
Database
ISI
SICI code
0021-5198(200010)84:2<146:EOE(OH>2.0.ZU;2-7
Abstract
It was previously found that human chymase cleaves big endothelins (ETs) at the Tyr(31)-Gly(32) bond and produces 31-amino acid ETs (1-31). In the pre sent study, human plasma concentrations of ET-1 (1-31) and ET-1 were examin ed and the effect of synthetic ET-1 (1-31) on the proliferation of cultured human mesangial cells (HMCs) was investigated. The proliferative effect of ET-1 (1-31) was evaluated from the [H-3]-thymidine uptake. The activity of extracellular signal-regulated kinase (ERK) and DNA binding activity of ac tivator protein-1 were determined by using an in-gel kinase assay and gel m obility shift assay, respectively. Immunoreactive ET-1 (1-31) was detectabl e in plasma, but the level was slightly lower than that of ET-1. ET-1 (1-31 ) increased [H-3]-thymidine incorporation in HMCs to a degree similar to th at induced by ET-1. ET-1 (1-31) also activated ERK1/2. Inhibition of protei n kinase C and ERK kinase caused a reduction of ET-1 (1-31)-induced ERK1/2 activation. The ERK1/2 activation was followed by an increase in transcript ion factor activator protein-1 DNA binding activity. These findings suggest that ET-1 (1-31) is a bioactive peptide in humans and ET-1 (1-31) itself s timulates HMC proliferation.