Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea.
THERABEST, Co, Inc, Seoul, Korea.
J Drug Target. 2022 Aug;30(7):792-799. doi: 10.1080/1061186X.2022.2069781. Epub 2022 Jun 13.
Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterised by irreversible fibrosis and destruction of the alveolar structure. Receptor for advanced glycation end products (RAGE) has been identified as one of the key molecules involved in IPF pathogenesis. A RAGE-antagonist peptide (RAP) was developed based on the RAGE-binding domain of high mobility group box-1 (HMGB-1). Anti-IPF effects of RAP were evaluated in a bleomycin-induced mouse model of IPF. Bleomycin was administered intratracheally, and then RAP was administrated twice by intratracheal instillation, 1 and 3 d after bleomycin challenge. Seven days after the bleomycin challenge, the mice were sacrificed and the lungs were harvested. The results showed that pulmonary hydroxyproline was reduced in mice administered RAP compared with the control group. Tumour growth factor-β (TGF-β), α-smooth muscle actin (α-SMA) and collagen were also reduced by RAP administration in a dose-dependent manner. Longer-term effects of RAP were investigated in mice challenged with bleomycin. RAP was administered intratracheally every 7 d for 28 d, after which lung samples were harvested and analysed. The results showed that hydroxyproline, TGF-β, α-SMA and collagen were reduced by repeated RAP administration. Taken together, the results suggest that RAP is useful for treatment of IPF.
特发性肺纤维化（IPF）是一种以不可逆纤维化和肺泡结构破坏为特征的间质性肺疾病。晚期糖基化终产物（RAGE）受体已被确定为参与 IPF 发病机制的关键分子之一。基于高迁移率族蛋白 B1（HMGB-1）的 RAGE 结合域，开发了一种 RAGE 拮抗剂肽（RAP）。在博来霉素诱导的 IPF 小鼠模型中评估了 RAP 的抗 IPF 作用。通过气管内给药博来霉素，然后在博来霉素挑战后 1 和 3 天通过气管内滴注两次给予 RAP。博来霉素挑战后 7 天，处死小鼠并采集肺部。结果表明，与对照组相比，RAP 给药组小鼠肺羟脯氨酸减少。RAP 给药还以剂量依赖性方式减少肿瘤生长因子-β（TGF-β）、α-平滑肌肌动蛋白（α-SMA）和胶原蛋白。在接受博来霉素挑战的小鼠中研究了 RAP 的长期作用。RAP 每隔 7 天经气管内给药 28 天，然后采集肺样本并进行分析。结果表明，羟脯氨酸、TGF-β、α-SMA 和胶原蛋白通过重复 RAP 给药减少。总之，这些结果表明 RAP 可用于治疗 IPF。
