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Endothelin-1 triggers human peritoneal mesothelial cells' proliferation via ERK1/2-Ets-1 signaling pathway and contributes to endothelial cell angiogenesis.

Abstract：

BACKGROUND:Dysfunction of the peritoneum as a dialysis organ may result from progressive membrane injury on peritoneal dialysis (PD). It has been increasingly recognized that the human peritoneal mesothelial cells (HPMCs) play a key role in peritoneal membrane early injury. Recently, it has been reported that bioincompatible PD fluid with high concentrations of glucose and glucose degradation products, low pH, high osmolality, and peritonitis stimulates HPMCs to release endothelin-1 (ET-1). ET-1 causes increased the release of vascular endothelial growth factor, which is important for tumor cell angiogenesis. We hypothesized that activating ET-1 might predict injury of peritoneal membrane. METHODS:HPMCs were isolated from normal omentum. ERK1/2 and Ets-1 phosphorylation were measured by Western blot analysis. HPMC proliferation was detected by the bromodeoxyuridine (BrdU) assay. Capillary networks of tubes formed were photographed under a microscope, and five randomly selected fields from each well were analyzed for total capillary length by using Image J software. RESULTS:MEK-1 blocker significantly abolished the ERK1/2 activation by ET-1, which also triggered phosphorylation, thus activating the transcription factor Ets-1 downstream from ERK1/2. ET-1 was capable to induce HPMC proliferation, which could be attenuated by ET-1 antagonists. Antibody and small interfering RNA mediated blockade of Ets-1 had similar antiproliferative effects. Thus, ET-1 specifically triggered HPMC proliferation via ERK1/2-Ets-1 signaling pathway. VEGF production and endothelial cell angiogenesis were significantly in response to conditioned medium from HPMCs treated with ET-1. CONCLUSIONS:ET-1 triggered HPMC proliferation through the ERK1/2-Ets-1 signaling pathway and contributed to VEGF production and endothelial cell angiogenesis.

journal_name

J Cell Biochem

journal_title

Journal of cellular biochemistry

authors

Zhu N,Gu L,Jia J,Wang X,Wang L,Yang M,Yuan W

doi

10.1002/jcb.27631

subject

Has Abstract

pub_date

2019-03-01 00:00:00

pages

3539-3546

issue

eissn

0730-2312

issn

1097-4644

journal_volume

120

pub_type

杂志文章

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Endothelin-1 triggers human peritoneal mesothelial cells' proliferation via ERK1/2-Ets-1 signaling pathway and contributes to endothelial cell angiogenesis.