Blockade of the pentraxin 3/CD44 interaction attenuates lung injury‐induced fibrosis

Chi, Jhih-Ying; Hsiao, Yu-Wei; Liang, Hongbao; Huang, Tang Hsiu; Chen, Feng-Wei; Chen, Chenyang; Ko, Chiung-Yuan; Cheng, Chao-Chun; Wang, Ju‐Ming

doi:10.1002/ctm2.1099

Cited by 10 publications

(7 citation statements)

References 63 publications

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“…These data are consistent with a previous study in which Ptx3 promoted breast cancer stemness, migration, and invasion [ 19 ]. More importantly, it is reportedly that the Ptx3 can bind to CD44 transmembrane receptor in lung fibroblasts to activate fibrotic scar-related gene expression, such as fibronectin, collagen I, and α-SMA [ 16 ]. Given the relationship between Ptx3 and fibrotic scar formation in spinal cord injury, we speculate that Ptx3 can activate meningeal fibroblasts to express fibrotic scar-related gene expression through CD44 pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, secreted Ptx3 in the extracellular environment promotes surrounding cell migration [13], inflammation [14], and is correlated with fibrosis [15]. Currently, it has been reported that Ptx3 activates lung fibroblasts to differentiate myofibroblasts through binding to CD44 in which increase ECM deposition and express fibrotic markers (e.g., fibronectin, collagen I, and α-SMA) to form fibrotic scar [16]. However, the molecular mechanism whereby Ptx3 affects fibrotic scar formation after contusive spinal cord injury has yet to be examined.…”

Section: Introductionmentioning

confidence: 99%

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Astrocytic Cebpd Regulates Pentraxin 3 Expression to Promote Fibrotic Scar Formation After Spinal Cord Injury

Wang

Hsu

et al. 2023

Mol Neurobiol

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Astroglial-fibrotic scars resulted from spinal cord injury affect motor and sensory function, leading to paralysis. In particular, the fibrotic scar is a main barrier that disrupts neuronal regeneration after spinal cord injury. However, the association between astrocytes and fibrotic scar formation is not yet understood. We have previously demonstrated that the transcriptional factor Cebpd contributes to astrogliosis, which promotes glial scar formation after spinal cord injury. Herein, we show that fibrotic scar formation was decreased in the epicenter region in Cebpd−/− mice after contusive spinal cord injury and astrocytic Cebpd promoted fibroblast migration through secretion of Ptx3. Furthermore, the expression of Mmp3 was increased under recombinant protein Ptx3 treatment in fibroblasts by observing microarray data, resulting in fibroblast migration. In addition, regulation of Mmp3 occurs through the NFκB signaling pathway by using an irreversible inhibitor of IκBα phosphorylation in pretreated fibroblasts. Of note, we used the synthetic peptide RI37, which blocks fibroblast migration and decreases fibroblast Mmp3 expression in IL-1β-treated astrocyte conditioned media. Collectively, our data suggest that fibroblast migration can be affected by astrocytic Cebpd through the Ptx3/NFκB/Mmp3 axis pathway and that the RI37 peptide may act as a therapeutic medicine to inhibit fibrotic scar formation after spinal cord injury.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Astrocytic Cebpd Regulates Pentraxin 3 Expression to Promote Fibrotic Scar Formation After Spinal Cord Injury

Wang

Hsu

et al. 2023

Mol Neurobiol

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“…Pentraxin-3 is a component of the innate immune system and participates in resistance to inflammation and microorganisms (42). It is induced by primary proinflammatory cytokines, mainly IL-1 and tumor necrosis factor-α, and toll-like receptor agonists in different cell types, such as myeloid (mononuclear phagocytes, neutrophils, and dendritic cells), endothelial and stromal cells (46).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of CYFRA 21-1, Angiopoetin-2, Pentraxin-3, sRAGE, IL-6 and IL-10 in polytraumatized patients with concomitant thoracic trauma - helpful markers to predict pneumonia?

Vollrath,

Schindler,

Herrmann

et al. 2023

Shock

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Background Pneumonia is a frequent complication after polytrauma. This study aims to evaluate the ability of different serum markers to identify patients at risk of developing pneumonia after polytrauma. Methods A retrospective analysis of prospectively collected data in polytraumatized patients with concomitant thoracic trauma (ISS ≥16, AISThorax ≥ 3) was performed. The study cohort was divided into patients with and without pneumonia during the clinical course. Serum levels of lung epithelial (CYFRA 21-1), endothelial (Ang-2) and inflammatory (PTX-3, sRAGE, IL-6, IL-10) markers were measured upon arrival in the trauma room and on days two and five. Results A total of 73 patients and 16 healthy controls were included in this study. Of these, 20 patients (27.4%) developed pneumonia. Polytraumatized patients showed significantly increased CYFRA 21-1 levels with a distinct peak after admission compared to healthy controls. Serum PTX-3 significantly increased on day two in polytraumatized patients compared to healthy controls. ISS and demographic parameters were comparable between both groups (pneumonia vs. no pneumonia). No statistically significant difference could be observed for serum levels of CYFRA 21-1, Ang-2, PTX-3, sRAGE, IL-6 and IL-10 between the groups (pneumonia vs. no pneumonia) on all days. Logistic regression revealed a combination of IL-6, IL-10, sRAGE and PTX-3 to be eventually helpful to identify patients at risk of developing pneumonia and our newly developed score was significantly higher on day 0 in patients developing pneumonia (p < 0.05). Conclusion The investigated serum markers alone are not helpful to identify polytraumatized patients at risk of developing pneumonia, whilst a combination of IL-6, IL-10, PTX-3 and sRAGE might be.

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“…Masson’s trichrome staining is commonly used to detect collagen fiber formation in tissues [ 52 ]. The formation of collagen fibers was evaluated using Masson’s trichrome staining, per the manufacturer’s instructions.…”

Section: Methodsmentioning

confidence: 99%

“…Cell viability was measured using CCK-8 [ 52 , 54 ] (CCK-8, Dojindo, Japan), per the manufacturer’s protocols. Briefly, MRC-5 cells were seeded in 96-well plates (1.5 × 10 4 ) for 24 h. Then, the cells were serum starved in serum-free medium for 24 h. Next, the Prophylactic administration cells were incubated in MEM containing different CEP concentrations (0, 0.1, 0.2, 0.4, 0.8, 1, 2, 4, 8, and 16 μg/mL) for 1 h. Cells were subsequently exposed to 10 ng/mL TGF-β1 with or without CEP for 48 h. In contrast, for therapeutic administration, cells were exposed to 10 ng/mL TGF-β1 for 1 h, followed by the same CEP as prophylactic administration, and continued to be cultured for 48 h. Next, the media was replaced with MEM supplemented with 10% CCK-8 reagent, 100 μL of basal medium (MEM supplemented with 100 U/mL penicillin, 100 μg/mL streptomycin and Earle’s Balanced Salt Solution) mixed with CCK8 dye was added to the wells (CCK8 dye: MEM basal medium = 1:10), and the cells were cultured for another 2 h at 37 °C.…”

Section: Methodsmentioning

confidence: 99%

Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation

Chen¹,

Li²,

Liu³

et al. 2023

Molecules

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Pulmonary fibrosis (PF) is one of the sequelae of Corona Virus Disease 2019 (COVID-19), and currently, lung transplantation is the only viable treatment option. Hence, other effective treatments are urgently required. We investigated the therapeutic effects of an approved botanical drug, cepharanthine (CEP), in a cell culture model of transforming growth factor-β1 (TGF-β1) and bleomycin (BLM)-induced pulmonary fibrosis rat models both in vitro and in vivo. In this study, CEP and pirfenidone (PFD) suppressed BLM-induced lung tissue inflammation, proliferation of blue collagen fibers, and damage to lung structures in vivo. Furthermore, we also found increased collagen deposition marked by α-smooth muscle actin (α-SMA) and Collagen Type I Alpha 1 (COL1A1), which was significantly alleviated by the addition of PFD and CEP. Moreover, we elucidated the underlying mechanism of CEP against PF in vitro. Various assays confirmed that CEP reduced the viability and migration and promoted apoptosis of myofibroblasts. The expression levels of myofibroblast markers, including COL1A1, vimentin, α-SMA, and Matrix Metallopeptidase 2 (MMP2), were also suppressed by CEP. Simultaneously, CEP significantly suppressed the elevated Phospho-NF-κB p65 (p-p65)/NF-κB p65 (p65) ratio, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) levels, and elevated inhibitor of NF-κB Alpha (IκBα) degradation and reversed the progression of PF. Hence, our study demonstrated that CEP prevented myofibroblast activation and treated BLM-induced pulmonary fibrosis in a dose-dependent manner by regulating nuclear factor kappa-B (NF-κB)/ NLRP3 signaling, thereby suggesting that CEP has potential clinical application in pulmonary fibrosis in the future.

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Blockade of the pentraxin 3/CD44 interaction attenuates lung injury‐induced fibrosis

Abstract: 1. PTX3 promotes fibroblast activation and pulmonary fibrosis. 2. CD44 mediates PTX3-induced fibrotic activation and regulation in lung injury. 3. αPTX3i is a novel and promising candidate for fILD therapy.

Cited by 10 publications

References 63 publications

Astrocytic Cebpd Regulates Pentraxin 3 Expression to Promote Fibrotic Scar Formation After Spinal Cord Injury

Astrocytic Cebpd Regulates Pentraxin 3 Expression to Promote Fibrotic Scar Formation After Spinal Cord Injury

Evaluation of CYFRA 21-1, Angiopoetin-2, Pentraxin-3, sRAGE, IL-6 and IL-10 in polytraumatized patients with concomitant thoracic trauma - helpful markers to predict pneumonia?

Cepharanthine Ameliorates Pulmonary Fibrosis by Inhibiting the NF-κB/NLRP3 Pathway, Fibroblast-to-Myofibroblast Transition and Inflammation

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