Xia Yong, Cheng Mei, Hu Yanyan, Li Man, Shen Lin, Ji Xiang, Cui Xiaopei, Liu Xiangju, Wang Weiling, Gao Haiqing
Department of Geriatric Medicine, Qilu Hospital of Shandong University, Jinan, China.
Shandong provincial Key Laboratory of Cardiovascular Proteomics, Shandong University, Jinan, China.
Ann Transl Med. 2021 Sep;9(18):1424. doi: 10.21037/atm-21-3777.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease that leads to respiratory failure, and for which there is no effective treatment. Apolipoprotein A-1 (ApoA-1) has been reported to ameliorate the bleomycin (BLM)-induced IPF model.
To examine the function of D-4F, an ApoA-1 mimetic polypeptide, in IPF, we used an BLM-induced model. We assigned mice into the following 3 groups: the Blank Group (BLK Group), the Bleomycin Treatment Group (Model Group), and the D-4F Interference Group (Inter Group). The BLM-induced fibrosis was examined by hematoxylin and eosin, Masson's trichrome (M-T) staining and immunohistochemical staining. An untargeted lipidomic and transcriptomic analysis were used to examine the function of D-4F.
There were 35 differentially altered lipids (DALs) in the BLK, Model and Inter Groups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that glycerophospholipid metabolism was the most highly enriched of the 35 DALs. There were 99 differentially expressed genes (DEGs) in the BLK, Model and Inter Groups. The enriched KEGG pathway analysis showed that the mitogen-activated protein kinase (MAPK) pathway was 1 of the top 10 pathways. The results of the untargeted lipidomic and transcriptomic analysis showed that phospholipase A2 group 4c (Pla2g4c) was a crucial gene in both the MAPK pathway and glycerophospholipid metabolism. Pla2g4c was increased in the Model Group but decreased in the Inter Group.
It may be that D-4F prevented the BLM-induced pulmonary fibrosis model by inhibiting the expression of pla2g4c. Our findings suggest that D-4F may be a potential treatment of IPF.
特发性肺纤维化（IPF）是一种导致呼吸衰竭的进行性肺部疾病，目前尚无有效治疗方法。据报道，载脂蛋白A-1（ApoA-1）可改善博来霉素（BLM）诱导的IPF模型。
为研究载脂蛋白A-1模拟多肽D-4F在IPF中的作用，我们采用了博来霉素诱导的模型。将小鼠分为以下3组：空白组（BLK组）、博来霉素治疗组（模型组）和D-4F干预组（干预组）。通过苏木精-伊红染色、Masson三色染色（M-T）和免疫组化染色检测博来霉素诱导的纤维化。采用非靶向脂质组学和转录组学分析来研究D-4F的作用。
BLK组、模型组和干预组中有35种脂质差异改变（DALs）。京都基因与基因组百科全书（KEGG）通路分析显示，甘油磷脂代谢是35种DALs中富集程度最高的。BLK组、模型组和干预组中有99个差异表达基因（DEGs）。KEGG通路富集分析显示，丝裂原活化蛋白激酶（MAPK）通路是前10条通路之一。非靶向脂质组学和转录组学分析结果显示，磷脂酶A2第4c组（Pla2g4c）是MAPK通路和甘油磷脂代谢中的关键基因。Pla2g4c在模型组中升高，但在干预组中降低。
D-4F可能通过抑制Pla2g4c的表达来预防博来霉素诱导的肺纤维化模型。我们的研究结果表明，D-4F可能是IPF的一种潜在治疗方法。
