Journal Article

The role of FGF-2 in smoke-induced emphysema and the therapeutic potential of recombinant FGF-2 in patients with COPD

Kim, Yoon-Keun, Jee, Young-Koo, Oh, Yeon-Mok, Hong, Goohyeon, Kim, Young Min, Kim, You-Sun, Kim, Doh Hyung

2018

Overview

Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P   =  0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD ( n  = 6) resulted in significantly improved respiratory symptoms compared with baseline levels ( P   <  0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke. Lung disease: Inhaling a protein might help Studies on the role of the protein ‘fibroblast growth factor-2’ (FGF-2) in chronic obstructive pulmonary disease (COPD) suggest that inhaled FGF-2 could help treat the emphysema linked to smoking. Researchers in South Korea led by Young-Koo Jee at Dankook University, Cheonan, and Yeon-Mok Oh at the University of Ulsan, Seoul, studied the role of the reduced FGF-2 levels found in mice with lung inflammation caused by exposure to cigarette smoke. They also uncovered details of a protective effect of inhaled FGF-2, identifying specific cellular and lung structure changes attributed to the administered FGF-2. Reduced FGF-2 levels were also found in patients with COPD. Initial trials revealed some improvement in patients treated with FGF-2, but not at a statistically significant level. Nevertheless, the authors suggest their results justify further investigation of the protein’s therapeutic potential.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group,생화학분자생물학회
• Subject: 13 / 13/2 / 631/45/320 / 64 / 64/60 / 692/308/1426 / Administration, Intranasal / Aged / Alveoli / Animal models / Animals / Biomedical and Life Sciences / Biomedicine / Chronic obstructive pulmonary disease / Cigarette smoke / Elastase / Emphysema / Female / Fibroblast growth factor 2 / Fibroblast Growth Factor 2 - administration & dosage / Fibroblast Growth Factor 2 - metabolism / Fibroblast Growth Factor 2 - therapeutic use / Humans / Inflammation / Lung - metabolism / Lung diseases / Lungs / Macrophages / Macrophages - metabolism / Male / Medical Biochemistry / Mice / Mice, Inbred C57BL / Middle Aged / Molecular Medicine / Obstructive lung disease / Pancreatic Elastase - toxicity / Patients / Pulmonary Disease, Chronic Obstructive - drug therapy / Pulmonary Disease, Chronic Obstructive - metabolism / Pulmonary Emphysema - drug therapy / Pulmonary Emphysema - etiology / Pulmonary Emphysema - metabolism / Respiratory function / Statistical analysis / Stem Cells / Tobacco Smoke Pollution - adverse effects / 생화학