Resistin-like molecule-β in scleroderma-associated pulmonary hypertension

Daniel J. Angelini, Qingning Su, Kazuyo Yamaji-Kegan, Chunling Fan, Xingwu Teng, Paul M. Hassoun, Stephen C. Yang, Hunter C. Champion, Rubin M. Tuder, Roger A. Johns

Research output: Contribution to journalArticlepeer-review

Abstract

Scleroderma is a systemic, mixed connective tissue disease that can impact the lungs through pulmonary fibrosis, vascular remodeling, and the development of pulmonary hypertension and right heart failure. Currently, little is known about the molecular mechanisms that drive this condition,butwehave recently identified a novel gene product that is up-regulated in a murine model of hypoxia-induced pulmonary hypertension. This molecule, known as hypoxia-induced mitogenic factor (HIMF), is amember of the newly described resistin gene family. We have demonstrated that HIMF has mitogenic, angiogenic, vasoconstrictive, inflammatory, and chemokine-like properties, all of which are associated with vascular remodeling in the lung. Here, we demonstrate that the human homolog of HIMF, resistin-like molecule (RELM)-β, is expressed in the lung tissue of patients with scleroderma-associated pulmonary hypertension and is up-regulated compared with normal control subjects. Immunofluorescence colocalization revealed that RELM-β is expressed in the endothelium and vascular smooth muscle of remodeled vessels, as well as in plexiform lesions, macrophages, T cells, and myofibroblast-like cells. We also show that addition of recombinant RELM-β induces proliferation and activation of ERK1/2 in primary cultured human pulmonary endothelial and smooth muscle cells. These results suggest that RELM-β may be involved in the development of scleroderma-associated pulmonary hypertension.

Original languageEnglish (US)
Pages (from-to)553-561
Number of pages9
JournalAmerican journal of respiratory cell and molecular biology
Volume41
Issue number5
DOIs
StatePublished - 2009

Keywords

  • Hypoxia-induced mitogenic factor
  • Pulmonary hypertension
  • Resistin-like molecule β
  • Scleroderma
  • T helper type 2

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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