FIZZ1/RELMα, a novel hypoxia-induced mitogenic factor in lung with vasoconstrictive and angiogenic properties

Xingwu Teng, Dechun Li, Hunter C. Champion, Roger A Johns

Research output: Contribution to journalArticle

Abstract

In a mouse chronic hypoxia model of pulmonary hypertension, we discovered a novel hypoxia-inducible gene in lung, FIZZ1/RELMα, first through a cDNA array analysis and then confirmed by RT-PCR. Western blot and immunohistochemistry revealed that its expression was induced by hypoxia only in lung. The hypoxia-upregulated gene expression was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. 3H-thymidine incorporation demonstrated that the recombinant protein stimulated rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently ranging from 33×10-9 to 3.3×10-8 mol/L. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 μmol/L) inhibited HIMF-activated Akt phosphorylation. It also inhibited HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. Further studies showed that HIMF had angiogenic and vasoconstrictive properties. HIMF increased pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.

Original languageEnglish (US)
Pages (from-to)1065-1067
Number of pages3
JournalCirculation Research
Volume92
Issue number10
DOIs
StatePublished - May 30 2003

Fingerprint

Lung
Phosphatidylinositol 3-Kinase
Smooth Muscle Myocytes
Hypoxia
Phosphorylation
Cell Proliferation
Alveolar Epithelial Cells
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Angiogenesis Inducing Agents
Endothelin-1
Oligonucleotide Array Sequence Analysis
Recombinant Proteins
Pulmonary Hypertension
Angiotensin II
Vascular Resistance
Thymidine
Genes
Arterial Pressure
Western Blotting
Epithelial Cells

Keywords

  • Akt
  • Angiogenesis
  • Hypoxia-induced mitogenic factor
  • Proliferation
  • Vasoconstriction

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

FIZZ1/RELMα, a novel hypoxia-induced mitogenic factor in lung with vasoconstrictive and angiogenic properties. / Teng, Xingwu; Li, Dechun; Champion, Hunter C.; Johns, Roger A.

In: Circulation Research, Vol. 92, No. 10, 30.05.2003, p. 1065-1067.

Research output: Contribution to journalArticle

@article{e94de3d8971c4b13ac3b37e4e499adf0,
title = "FIZZ1/RELMα, a novel hypoxia-induced mitogenic factor in lung with vasoconstrictive and angiogenic properties",
abstract = "In a mouse chronic hypoxia model of pulmonary hypertension, we discovered a novel hypoxia-inducible gene in lung, FIZZ1/RELMα, first through a cDNA array analysis and then confirmed by RT-PCR. Western blot and immunohistochemistry revealed that its expression was induced by hypoxia only in lung. The hypoxia-upregulated gene expression was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. 3H-thymidine incorporation demonstrated that the recombinant protein stimulated rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently ranging from 33×10-9 to 3.3×10-8 mol/L. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 μmol/L) inhibited HIMF-activated Akt phosphorylation. It also inhibited HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. Further studies showed that HIMF had angiogenic and vasoconstrictive properties. HIMF increased pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.",
keywords = "Akt, Angiogenesis, Hypoxia-induced mitogenic factor, Proliferation, Vasoconstriction",
author = "Xingwu Teng and Dechun Li and Champion, {Hunter C.} and Johns, {Roger A}",
year = "2003",
month = "5",
day = "30",
doi = "10.1161/01.RES.0000073999.07698.33",
language = "English (US)",
volume = "92",
pages = "1065--1067",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - FIZZ1/RELMα, a novel hypoxia-induced mitogenic factor in lung with vasoconstrictive and angiogenic properties

AU - Teng, Xingwu

AU - Li, Dechun

AU - Champion, Hunter C.

AU - Johns, Roger A

PY - 2003/5/30

Y1 - 2003/5/30

N2 - In a mouse chronic hypoxia model of pulmonary hypertension, we discovered a novel hypoxia-inducible gene in lung, FIZZ1/RELMα, first through a cDNA array analysis and then confirmed by RT-PCR. Western blot and immunohistochemistry revealed that its expression was induced by hypoxia only in lung. The hypoxia-upregulated gene expression was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. 3H-thymidine incorporation demonstrated that the recombinant protein stimulated rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently ranging from 33×10-9 to 3.3×10-8 mol/L. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 μmol/L) inhibited HIMF-activated Akt phosphorylation. It also inhibited HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. Further studies showed that HIMF had angiogenic and vasoconstrictive properties. HIMF increased pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.

AB - In a mouse chronic hypoxia model of pulmonary hypertension, we discovered a novel hypoxia-inducible gene in lung, FIZZ1/RELMα, first through a cDNA array analysis and then confirmed by RT-PCR. Western blot and immunohistochemistry revealed that its expression was induced by hypoxia only in lung. The hypoxia-upregulated gene expression was located in the pulmonary vasculature, bronchial epithelial cells, and type II pneumocytes. 3H-thymidine incorporation demonstrated that the recombinant protein stimulated rat pulmonary microvascular smooth muscle cell (RPSM) proliferation dose-dependently ranging from 33×10-9 to 3.3×10-8 mol/L. Therefore, we renamed this gene as hypoxia-induced mitogenic factor (HIMF). HIMF strongly activated Akt phosphorylation. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 (10 μmol/L) inhibited HIMF-activated Akt phosphorylation. It also inhibited HIMF-stimulated RPSM proliferation. Thus, the PI3K/Akt pathway, at least in part, mediates the proliferative effect of HIMF. Further studies showed that HIMF had angiogenic and vasoconstrictive properties. HIMF increased pulmonary arterial pressure and vascular resistance more potently than either endothelin-1 or angiotensin II.

KW - Akt

KW - Angiogenesis

KW - Hypoxia-induced mitogenic factor

KW - Proliferation

KW - Vasoconstriction

UR - http://www.scopus.com/inward/record.url?scp=0038390235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038390235&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000073999.07698.33

DO - 10.1161/01.RES.0000073999.07698.33

M3 - Article

VL - 92

SP - 1065

EP - 1067

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 10

ER -