Comprehensive lipid profiling of bleomycin‐induced lung injury

Saito, Kosuke; Tanaka, Nozomi; Ikari, Jun; Suzuki, Masaki; Anazawa, Rie; Abe, Mitsuhiro; Saito, Yoshiro

doi:10.1002/jat.3758

Cited by 16 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Further, it was reported that PI binds to the CD14 plasma membrane and prevents monocyte activation by bacterial lipopolysaccharides (40). Saito et al (15) conjectured that high levels of PG and PI counteract inflammation and thus ameliorate BLM-induced lung injury . Our study showed that PG and PI were more increased in the Inter Group than the Model Group , and D-4F can decrease inflammation in experimental asthma and influenza infection.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Combined transcriptomic and lipidomic analysis of D-4F ameliorating bleomycin-induced pulmonary fibrosis

Xia¹,

Cheng²,

Hu³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

Background: 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. Methods:To examine the function of D-4F, an ApoA-1 mimetic polypeptide, in IPF, we used an in-vivo 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.Results: 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.Conclusions: 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.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The way of induction of lung fibrosis is as the article described (15). To induce pulmonary fibrosis, the mice were anesthetized with pentobarbital sodium salt and given a single intratracheal instillation of 60 μL (2 mg/kg) or PBS as a control.…”

Section: Induction Of Lung Fibrosismentioning

confidence: 99%

Combined transcriptomic and lipidomic analysis of D-4F ameliorating bleomycin-induced pulmonary fibrosis

Xia¹,

Cheng²,

Hu³

et al. 2021

Ann Transl Med

View full text Add to dashboard Cite

show abstract

“…Similarly, human studies have reported seemingly contradictory data regarding the direction and magnitude of change in surfactant lipids during disease, and there is no agreement on a mechanism for the observed alterations [67] (Table 1). In some studies, increased levels of PC, cholesterol and bis monoacyl phosphoglycerate (BMP) in whole lung tissue and of all lipids in BAL up to 21 days after bleomycin have been reported [131]. Intratracheally administered bleomycin increased cholesterol and free FA in BAL in rats, and this was associated with increased collagen deposition and epithelial cell proliferation, elastic recoil and surface tension of the BAL.…”

Section: Lipids In Interstitial Lung Disease and Idiopathic Pulmonarymentioning

confidence: 99%

Alveolar lipids in pulmonary disease. A review

2020

View full text Add to dashboard Cite

Lung lipid metabolism participates both in infant and adult pulmonary disease. The lung is composed by multiple cell types with specialized functions and coordinately acting to meet specific physiologic requirements. The alveoli are the niche of the most active lipid metabolic cell in the lung, the type 2 cell (T2C). T2C synthesize surfactant lipids that are an absolute requirement for respiration, including dipalmitoylphosphatidylcholine. After its synthesis and secretion into the alveoli, surfactant is recycled by the T2C or degraded by the alveolar macrophages (AM). Surfactant biosynthesis and recycling is tightly regulated, and dysregulation of this pathway occurs in many pulmonary disease processes. Alveolar lipids can participate in the development of pulmonary disease from their extracellular location in the lumen of the alveoli, and from their intracellular location in T2C or AM. External insults like smoke and pollution can disturb surfactant homeostasis and result in either surfactant insufficiency or accumulation. But disruption of surfactant homeostasis is also observed in many chronic adult diseases, including chronic obstructive pulmonary disease (COPD), and others. Sustained damage to the T2C is one of the postulated causes of idiopathic pulmonary fibrosis (IPF), and surfactant homeostasis is disrupted during fibrotic conditions. Similarly, surfactant homeostasis is impacted during acute respiratory distress syndrome (ARDS) and infections. Bioactive lipids like eicosanoids and sphingolipids also participate in chronic lung disease and in respiratory infections. We review the most recent knowledge on alveolar lipids and their essential metabolic and signaling functions during homeostasis and during some of the most commonly observed pulmonary diseases.

show abstract

“…The NLRP3inflammasome consists of three elements including the NLRP3, procaspase 1 and the apoptosis speck-like protein (ASC) containing a caspase recruitment domain (CARD), which links NLRP3 with procaspase 1 (Robert et al, 2016). In order to generate full activation of the inflammasome complex usually two independent signals are needed (Figure 3): (1) a NFκβ priming signal TLR-4 signaling [enhanced by lipopolysaccharide (LPS) or oxidized phospholipid species] or the presence of cholesterol crystals (Bauernfeind et al, 2009;Ertunc and Hotamisligil, 2016;Fessler and Summer, 2016;Nakayama, 2018;Saito et al, 2019) and;…”

Section: Inflammatory Response Under Impaired Lung Mechanics -Where Smentioning

confidence: 99%

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Treumann

Baumjohann

2020

Front. Physiol.

View full text Add to dashboard Cite

Sehlmeyer et al. SP-C/Cholesterol Relationships in Alveoli diffusion through lipid membranes is not well understood. However, it has been proposed that the interactions between cholesterol and the acyl carbon chains in phospholipids (stabilized by Van der Waals' forces) (Wennberg et al., 2012) create tightly packed arrangements that limits small molecule diffusion (Zocher et al., 2013). By decreasing trans-gauche rotation of the phospholipid acyl chains, membrane rigidity increases (Cassera et al., 2002; Molugu and Brown, 2019) leading to less free volume and free pockets which may accommodate oxygen, therefore reducing its flux (its partition and diffusion) through membranes (Zuniga-Hertz and Patel, 2019). Mammals developed sophisticated organs to optimize the uptake of oxygen during the life essential breathing cycle. From conducting airways to the second biggest surface exposed to the environment, the alveolar human surface (Ochs et al., 2004). In addition, the first membrane that oxygen encounters in the mammalian lungs is a complex mixture of lipids (mainly phosphatidylcholines (PC), such as dipalmitoylphosphatidylcholine (DPPC), up to a 90%) and proteins (10%) with a 5-10% of cholesterol (14-20% mol) (Zuo et al., 2008; Bernhard, 2016), called lung surfactant (surface active agent). Interestingly two surfaces in the human body present with abnormally higher cholesterol molar ratio, and both of them are in contact with the environment tightly regulating the uptake of oxygen. On the one hand, as previously explained, lung surfactant presents around a 14-20% mol cholesterol in its composition. On the other hand the eye lens surface contains up to 35% mol of cholesterol (Raguz et al., 2008; Mainali et al., 2013), compared to a normal cell plasma membrane with a 0.5 phospholipid to cholesterol molar ratio (van Meer et al., 2008; Widomska et al., 2017). Although the main function of lung Abbreviations: α-SMA, alpha smooth muscle actin; aaAMs, alternatively activated alveolar macrophages; ABCA1, ATP binding cassette transporter A1; ABCG1, ATP binding cassette transporter G1; ADA, adenosine-deaminase; ADP, adenosine diphosphate; AEC, alveolar epithelial cell; AE1C, alveolar epithelial type 1 cell; AE2C, alveolar epithelial type 2 cell; ALI

show abstract

Comprehensive lipid profiling of bleomycin‐induced lung injury

Cited by 16 publications

References 44 publications

Combined transcriptomic and lipidomic analysis of D-4F ameliorating bleomycin-induced pulmonary fibrosis

Combined transcriptomic and lipidomic analysis of D-4F ameliorating bleomycin-induced pulmonary fibrosis

Alveolar lipids in pulmonary disease. A review

Alveolar Dynamics and Beyond – The Importance of Surfactant Protein C and Cholesterol in Lung Homeostasis and Fibrosis

Contact Info

Product

Resources

About