Resistin-like molecule α in allergen-induced pulmonary vascular remodeling

Chunling Fan, Lucas W. Meuchel, Qingning Su, Daniel J. Angelini, Ailan Zhang, Chris Cheadle, Irina Kolosova, Oleg D. Makarevich, Kazuyo Yamaji-Kegan, Marc E. Rothenberg, Roger A. Johns

Research output: Contribution to journalArticlepeer-review

Abstract

Resistin-like molecule α (RELMα) has mitogenic, angiogenic, vasoconstrictive, and chemokine-like properties and is highly relevant in lung pathology. Here, we used RELMα knockout (Retnla-/-) mice to investigate the role of RELMα in pulmonary vascular remodeling after intermittent ovalbumin (OVA) challenge. We compared saline- and OVA-exposed wild-type (WT) mice and found that OVA induced significant increases in right ventricular systolic pressure, cardiac hypertrophy, pulmonary vascular remodeling of intra-alveolar arteries, goblet cell hyperplasia in airway epithelium, and intensive lung inflammation, especially perivascular inflammation. Genetic ablation of Retnla prevented the OVA-induced increase in pulmonary pressure and cardiac hypertrophy seen in WT mice. Histological analysis showed that Retnla-/- mice exhibited less vessel muscularization, less perivascular inflammation, reduced medial thickness of intra-alveolar vessels, and fewer goblet cells in upper airway epithelium (250-600 μm) than did WT animals after OVA challenge. Gene expression profiles showed that genes associated with vascular remodeling, including those related to muscle protein, contractile fibers, and actin cytoskeleton, were expressed at a lower level in OVA-challenged Retnla-/- mice than in similarly treated WT mice. In addition, bronchoalveolar lavage from OVA-challenged Retnla-/- mice had lower levels of cytokines, such as IL-1β, -1 receptor antagonist, and -16, chemokine (C-X-C motif) ligand 1, -2, -9, -10, and -13, monocyte chemoattractant protein-1, macrophage colony-stimulating factor, TIMP metallopeptidase inhibitor-1, and triggering receptor expressed on myeloid cells-1, than did that from WT mice when analyzed by cytokine array dot blots. Retnla knockout inhibited the OVA-induced T helper 17 response but not the T helper 2 response. Altogether, our results suggest that RELMα is involved in immune response-induced pulmonary vascular remodeling and the associated increase in inflammation typically observed after OVA challenge.

Original languageEnglish (US)
Pages (from-to)303-313
Number of pages11
JournalAmerican journal of respiratory cell and molecular biology
Volume53
Issue number3
DOIs
StatePublished - Sep 1 2015

Keywords

  • Inflammation
  • Pulmonary hypertension
  • Resistin-like molecule α
  • T helper 17
  • Vascular remodeling

ASJC Scopus subject areas

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

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