title: Resistin-like molecule-beta in scleroderma-associated pulmonary hypertension.
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, but we have 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 a member 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)-beta, 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-beta 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-beta induces proliferation and activation of ERK1/2 in primary cultured human pulmonary endothelial and smooth muscle cells. These results suggest that RELM-beta may be involved in the development of scleroderma-associated pulmonary hypertension.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 361, Baltimore, MD 21205, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Angelini
authors.forename: Qingning
authors.initials: Q
authors.lastname: Su
authors.forename: Kazuyo
authors.initials: K
authors.lastname: Yamaji-Kegan
authors.forename: Chunling
authors.initials: C
authors.lastname: Fan
authors.forename: Xingwu
authors.initials: X
authors.lastname: Teng
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hassoun
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Yang
authors.forename: Hunter C
authors.initials: HC
authors.lastname: Champion
authors.forename: Rubin M
authors.initials: RM
authors.lastname: Tuder
authors.forename: Roger A
authors.initials: RA
authors.lastname: Johns
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D049109:Cell Proliferation; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008168:Lung / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011994:Recombinant Proteins / Q000378:metabolism; D012595:Scleroderma, Systemic / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; C486574:RETNLB protein, human; D011994:Recombinant Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3