Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis Partly by Inhibiting the Expression of LOX and LOXL-2

Xiang, Tong; Zhang, Shijie; Wang, Dongguang; Zhang, Li; Huang, Jingyun; Zhang, Tianli; Fan, Hong

doi:10.3389/fphar.2021.709819

Cited by 13 publications

(6 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TGF-β 1 /Smad2/3 and TNF-α/JNK signaling pathways are upstream pathways of LOX and regulate the activation of LOX [33][34][35][36] . Our results indicated that the increased expressions of TGF-β 1 and smad2/3 phosphorylation after BLM-stimulated was inhibited by Sch C administration in vivo.…”

Section: Discussionmentioning

confidence: 99%

Sch C Ameliorates Pulmonary Fibrosis by Inhibiting the Level of LOX

Zhao

Song

et al. 2023

Preprint

View full text Add to dashboard Cite

Pulmonary fibrosis (PF) is a serious progressive fibrotic disease that is characterized by excessive accumulation of extracellular matrix (ECM), thus resulting in stiff lung tissues. Lysyl oxidase (LOX) is an enzyme involved in fibrosis by catalyzing collagen cross-linking. Studies found that the ingredients in schisandra ameliorated bleomycin (BLM)-induced PF, but it is unknown whether the anti-PF of schisandra is related to LOX. In this study, we established models of PF including a mouse model stimulated by BLM and a HFL1 cell model induced by transforming growth factor (TGF)-β1 to evaluate the inhibition effects of Schisandrin C (Sch C) on PF. We observed that Sch C treatment decreased pulmonary indexes compared to control group. Treatment of Sch C showed a significant reduction in the accumulation of ECM as evidenced by decreased expressions of alpha-smooth muscle actin (α-SMA)、fibronectin (FN)、matrix metalloproteinases-2 (MMP2)、MMP9、tissue inhibitor of matrix metalloproteinases (TIMP1) and collagen proteins such as collagen 1A1 (Col 1A1), and Col 3A1. In addition, the expression of LOX in the lung tissue of mice after Sch C treatment was effectively decreased compared with the MOD group. The inhibition effects in vitro were consistent with those in vivo. Mechanistic studies revealed that Sch C significantly inhibited TGF-β1/Smad2/3 and TNF-α/JNK signaling pathways. In conclusion, our data demonstrated that Sch C significantly ameliorated PF in vivo and vitro, which may play an important role by reducing ECM deposition and inhibiting the production of LOX.

show abstract

Section: Discussionmentioning

confidence: 99%

Sch C Ameliorates Pulmonary Fibrosis by Inhibiting the Level of LOX

Zhao

Song

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…TGF-β 1 /Smad2/3 and TNF-α/JNK signaling pathways are upstream pathways of LOX and regulate the activation of LOX 38 – 41 . Our results indicated that the increased expressions of TGF-β 1 and smad2/3 phosphorylation after BLM-stimulated was inhibited by Sch C administration in vivo.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory effects of Schisandrin C on collagen behavior in pulmonary fibrosis

Xu,

Zhao,

Song

et al. 2023

Sci Rep

View full text Add to dashboard Cite

Pulmonary fibrosis (PF) is a serious progressive fibrotic disease that is characterized by excessive accumulation of extracellular matrix (ECM), thus resulting in stiff lung tissues. Lysyl oxidase (LOX) is an enzyme involved in fibrosis by catalyzing collagen cross-linking. Studies found that the ingredients in schisandra ameliorated bleomycin (BLM)-induced PF, but it is unknown whether the anti-PF of schisandra is related to LOX. In this study, we established models of PF including a mouse model stimulated by BLM and a HFL1 cell model induced by transforming growth factor (TGF)-β1 to evaluate the inhibition effects of Schisandrin C (Sch C) on PF. We observed that Sch C treatment decreased pulmonary indexes compared to control group. Treatment of Sch C showed a significant reduction in the accumulation of ECM as evidenced by decreased expressions of α-SMA, FN, MMP2, MMP9, TIMP1 and collagen proteins such as Col 1A1, and Col 3A1. In addition, the expression of LOX in the lung tissue of mice after Sch C treatment was effectively decreased compared with the MOD group. The inhibition effects in vitro were consistent with those in vivo. Mechanistic studies revealed that Sch C significantly inhibited TGF-β1/Smad2/3 and TNF-α/JNK signaling pathways. In conclusion, our data demonstrated that Sch C significantly ameliorated PF in vivo and vitro, which may play an important role by reducing ECM deposition and inhibiting the production of LOX.

show abstract

“…As described previously [ 54 ], lung micro-CT was conducted in all mice under isoflurane anesthesia using a Quantum GX micro-CT scanner (PerkinElmer, Inc., Waltham, MA) on day 21 after BLM administration. The parameters of the X-ray tube were 90 kVp and 160 μA, and projection radiographs were obtained during the entire 360° gantry rotation, which took approximately 4.5 minutes.…”

Section: Methodsmentioning

confidence: 99%

“…Primary lung fibroblasts were isolated from the mouse lung, purified, and identified as previously described [ 54 ]. Briefly, the lungs from suckling mice (one-week-old) were collected, washed well to remove blood, minced into small pieces (1×1×1 mm), and seeded in Dulbecco’s modified Eagle’s medium containing 10% FBS (Gibco, USA).…”

Section: Methodsmentioning

confidence: 99%

AAV9-Tspyl2 gene therapy retards bleomycin-induced pulmonary fibrosis by modulating downstream TGF-β signaling in mice

et al. 2023

Self Cite

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a devastating fibrotic lung disease characterized by scarring and destruction of the lung architecture, with limited treatment options. Targeted gene therapy to restore cell division autoantigen-1 (CDA1) expression may be a potential treatment approach to delay the progression of pulmonary fibrosis (PF). Here, we focused on CDA1, which was significantly decreased in human IPF, in a mouse model of bleomycin (BLM)-induced PF, and in transforming growth factor (TGF-β)-challenged lung fibroblasts. In vitro, CDA1 overexpression by lentivirus infection in human embryonic lung fibroblasts (HFL1 cells) inhibited the production of pro-fibrotic and pro-inflammatory cytokines, lung fibroblast-to-myofibroblast transition, and extracellular matrix protein expression induced by exogenous TGF‐β1 treatment, whereas CDA1 knockdown with small interfering RNA promoted this effect. CDA1 overexpression also inhibited cell proliferation and migration. In a mouse model of BLM-induced PF, we provided novel evidence that the intratracheal delivery of adeno-associated virus serotype 9 carrying the mouse Tspyl2 gene reduced lung tissue inflammation and fibrosis. Mechanistically, CDA1, as a transcription regulator, could repress the TGF-β signal transduction in vivo and in vitro. In conclusion, our results show that Tspyl2 gene therapy plays an antifibrotic role by inhibiting the lung fibroblast-to-myofibroblast transition and downstream TGF-β/Smad3 signaling transduction in BLM-induced PF in mice, suggesting that CDA1 is an appropriate and promising therapeutic target for PF.

show abstract

Azithromycin Attenuates Bleomycin-Induced Pulmonary Fibrosis Partly by Inhibiting the Expression of LOX and LOXL-2

Cited by 13 publications

References 60 publications

Sch C Ameliorates Pulmonary Fibrosis by Inhibiting the Level of LOX

Sch C Ameliorates Pulmonary Fibrosis by Inhibiting the Level of LOX

Inhibitory effects of Schisandrin C on collagen behavior in pulmonary fibrosis

AAV9-Tspyl2 gene therapy retards bleomycin-induced pulmonary fibrosis by modulating downstream TGF-β signaling in mice

Contact Info

Product

Resources

About