源自两栖动物的多肽 RL-RF10 可改善百草枯诱导的肺纤维化损伤-武汉天德生物科技有限公司

Biomedicine & Pharmacotherapy 171 (2024) 116184

https://doi.org/10.1016/j.biopha.2024.116184

Amphibian-derived peptide RL-RF10 ameliorates paraquat-induced pulmonary fibrosis injury

Huiling Sun ^a,¹ , Yutong Wu ^a,¹ , Ziqian Xiong ^a,¹ , Yuanqi Gu ^a,¹ , Qiuye Jia ^a , Zeqiong Ru ^a , Ying Peng ^a , Zijian Kang ^a , Yuansheng Li ^a , Yubing Huang ^c , Saige Yin ^a , Kun Guo ^a , Chengan Feng ^a , Jing Tang ^c , Zhenhua Gao ^d,e,**, Ying Wang ^b,^* , Xinwang Yang ^a,*

** Corresponding author at: Department of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China.

* Corresponding authors.

E-mail addresses: gaozhenhua@ydyy.cn (Z. Gao), wangying_814@163.com (Y. Wang), yangxinwang@kmmu.edu.cn, yangxinwanghp@163.com (X. Yang).

¹These authors contributed equally to this manuscript.

^a Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, 650500, China

^bKey Laboratory of Chemistry in Ethnic Medicinal Resources & Key Laboratory of Natural Products Synthetic Biology of Ethnic Medicinal Endophytes, State Ethnic Affairs Commission & Ministry of Education, School of Ethnic Medicine, Yunnan Minzu University, Kunming, Yunnan, 650504, China

^cDepartment of Biochemistry and Molecular Biology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, Yunnan, 650500, China

^dDepartment of Urology, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, China

^eYunnan Province Clinical Research Center for Chronic Kidney Disease, Kunming, Yunnan, 650032, China

摘要

肺纤维化是肺组织损伤后修复功能障碍的结果，其特点是成纤维细胞增殖和大量细胞外基质聚集。一旦出现纤维化病变，很难进行有效治疗，目前可用的药物也很少。在这里，我们发现了一种从青蛙皮肤分泌物中提取的短环十肽 RL-RF10，它是一种潜在的改善肺纤维化的新型先导分子。体内实验表明，RL-RF10能以浓度依赖的方式改善百草枯（PQ）诱导后的肺组织病理学损伤和纤维化。第7天，对小鼠进行的支气管肺泡灌洗液检测显示，RL-RF10通过降低肺组织中炎症相关因子（包括转化生长因子-β1（TGF-β1）和肿瘤坏死因子-α）的表达，发挥了抗炎作用。此外，RL-RF10 还能下调胶原蛋白 I、胶原蛋白 III 和波形蛋白的水平，同时增加 E-cadherin 的表达，从而抑制上皮-间质转化。进一步的研究表明，与 TGF-β1 密切相关的 SMAD2/3 信号通路在增强 RL-RF10 缓解肺纤维化的作用中发挥了关键作用。体内和体外试验均表明，在 PQ 诱导后，RLRF10 治疗可显著降低 SMAD2 和 SMAD3 的磷酸化水平。总之，我们研究了 RL-RF10 肽对肺纤维化的保护作用及其内在机制，并证明了它作为治疗肺纤维化疾病的新型候选药物的潜力。