Upregulation of receptor tyrosine kinase-like orphan receptor 2 in idiopathic pulmonary fibrosis

• Published in: The Korean journal of internal medicine Vol. 36; no. 4; pp. 914 - 923
• Main Authors: Son, Ji-Hye, Lee, Jong-Uk, Chin, Susie, Go, Eun-Suk, Park, Jai-Seong, Shin, Hwa-Kyun, Chang, Hun Soo, Park, Jong-Sook, Park, Choon-Sik
• Format: Journal Article
• Language: English
• Published: Korea (South) The Korean Association of Internal Medicine 01.07.2021; 대한내과학회
• Subjects: Bronchoalveolar Lavage Fluid; differential diagnosis; Humans; idiopathic pulmonary fibrosis; Idiopathic Pulmonary Fibrosis - genetics; Lung Diseases, Interstitial; Original; receptor tyrosine kinase-like orphan receptors; Receptor Tyrosine Kinase-like Orphan Receptors - genetics; Up-Regulation; 내과학; Bronchoalveolar lavage fluid; Differential diagnosis; Receptor tyrosine kinase-like orphan receptors; Idiopathic pulmonary fibrosis
• ISSN: 1226-3303; 2005-6648
• DOI: 10.3904/kjim.2019.270

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) is a major regulator of Wnt signaling, which is involved in fibroblast dysfunction. Because its role has not been evaluated in idiopathic pulmonary fibrosis (IPF), we examined the clinical implications of ROR2 expression. ROR2 mRNA expression was measured using reverse transcription polymerase chain reaction in lung tissue-derived fibroblasts from IPF patients (n = 14) and from controls (n = 10). ROR2 protein was measured using enzyme-linked immunosorbent assay in primary fibroblasts from IPF patients (n = 14) and controls (n = 10), and in bronchoalveolar lavage (BAL) fluids obtained from normal controls (NC; n = 30). IPF patients (n = 84), and other patients with interstitial lung diseases, including nonspecific interstitial pneumonia (NSIP; n = 10), hypersensitivity pneumonitis (HP; n = 10), and sarcoidosis (n = 10). ROR2 mRNA and protein levels were significantly higher in IPF fibroblasts than in controls (p = 0.003, p = 0.0017, respectively). ROR2 protein levels in BAL fluids from patients with IPF were significantly higher than in those from NC (p < 0.001), and from patients with NSIP (p = 0.006), HP (p = 0.004), or sarcoidosis (p = 0.004). Receiver operating characteristic curves showed a clear difference between IPF and NC in ROR2 protein level (area under the curve, 0.890; confidence interval, 0.829 to 0.950; p < 0.001). ROR2 protein levels were significantly higher in GAP stage III than in GAP stages I and II (p = 0.016). ROR2 may be related to the development of IPF, and its protein level may be a useful and severity-dependent candidate marker for IPF.