Canadian Respiratory Journal, 2020.2020, 3406530-0, DOI: https://doi.org/10.1155/2020/3406530

Upregulation of Potassium Voltage-Gated Channel Subfamily J Member 2 Levels in the Lungs of Patients with Idiopathic Pulmonary Fibrosis

Lee JU, Chang HS;Jung CA;Kim RH;Park CS;Park JS

Abstract

Background. Fibroblast dysfunction is the main pathogenic mechanism underpinning idiopathic pulmonary fibrosis (IPF). Potassium voltage-gated channel subfamily J member 2 (KCNJ2) plays critical roles in the proliferation of myofibroblasts and in the development of cardiac fibrosis.
Objectives. This study aimed to evaluate the role of KCNJ2 in IPF. Methods. KCNJ2 mRNA expression was measured using real-time PCR in fibroblasts from IPF patients and normal controls (NCs). Protein concentrations were measured by ELISA in bronchoalveolar lavage (BAL) fluid obtained from NCs (n = 30), IPF (n = 84), nonspecific interstitial pneumonia (NSIP; n = 9), hypersensitivity pneumonitis (HP; n = 8), and sarcoidosis (n = 10).
Results. KCNJ2 mRNA levels were significantly higher in fibroblasts from IPF (n = 14) than those from NCs (n = 10, ). KCNJ2 protein levels in BAL fluid were significantly higher in IPF (6.587 [1.441–26.01] ng/mL) than in NCs (0.084 [0.00–0.260] ng/mL, p < 0.001), NSIP (0.301 [0.070–5.059] ng/mL, p = 0.006), HP (0.365 [0.000–3.407] ng/mL, p = 0.02), and sarcoidosis (0.170 [0.057–1.179] ng/mL, p = 0.001). Receiver operating characteristic curves showed a clear difference between the IPF and NCs according to the KCNJ2 protein level (area under the curve = 0.893). The KCNJ2 protein cutoff level determined from the curves (0.636 ng/mL) showed a 90.0% specificity and 83.3% sensitivity in distinguishing IPF from NCs.
Conclusion. KCNJ2 may participate in the development of IPF, and its protein level may be a candidate diagnostic and therapeutic molecule for IPF.

• DOI: https://doi.org/10.1155/2020/3406530
• ISBN or ISSN: 1198-2241

• 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
• This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.