Open AccessEffect of Endothelin-1 (1-31) on Human Mesangial Cell Proliferation
Author(s) -
Masanori Yoshizumi,
Shoji Kubo,
Yuki Suzaki,
Koichiro Tsuchiya,
Hitoshi Hishida,
Tetsuhiro Hisayama,
Hirokazu Fukui,
Toshiaki Takahashi
Publication year - 2000
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.84.146
Subject(s) - microbiology and biotechnology , mesangial cell , activator (genetics) , protein kinase c , mapk/erk pathway , kinase , endothelins , cell growth , extracellular , protein kinase a , biology , chemistry , endothelin 1 , biochemistry , receptor , in vitro
It was previously found that human chymase cleaves big endothelins (ETs) at the Tyr31-Gly32 bond and produces 31-amino acid ETs (1-31). In the present study, human plasma concentrations of ET-1 (1-31) and ET-1 were examined 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 [3H]-thymidine uptake. The activity of extracellular signal-regulated kinase (ERK) and DNA binding activity of activator protein-1 were determined by using an in-gel kinase assay and gel mobility shift assay, respectively. Immunoreactive ET-1 (1-31) was detectable in plasma, but the level was slightly lower than that of ET-1. ET-1 (1-31) increased [3H]-thymidine incorporation in HMCs to a degree similar to that induced by ET-1. ET-1 (1-31) also activated ERK1/2. Inhibition of protein 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 transcription 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 stimulates HMC proliferation.