A novel multikinase inhibitor SKLB‐YTH‐60 ameliorates inflammation and fibrosis in bleomycin‐induced lung fibrosis mouse models

Liu, Hongyao; Wu, Xiuli; Chai, Guoqiang; Wang, Liqun; Wang, Guan; Yang, Lin; Liu, Zhihao; Wei, Wei; Su, Xingping; Zhang, Qianyu; Tan, Zhenhua; Yao, Yuqin; Ouyang, Liang; Yu, Luoting; Ye, Tinghong

doi:10.1111/cpr.13081

Cited by 17 publications

(11 citation statements)

References 37 publications

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“…TGF-β, epidermal growth factor (EGF), fibroblast growth factor (FGF), IL-1, connective tissue growth factor factors (CTGF), insulin-like growth factor-2 (IGF-2), nuclear factor-kb (NF-kB) and Wnt can activate the transcription factors SNAIL, TWIST1 and ZEB through a variety of cytokine pathways to directly initiate EMT ( Salton et al, 2019 ). FGFR1-3 inhibitor SKLB-YTH-60 ameliorates EMT and fibrosis in bleomycin-induced lung fibrosis mouse models ( Liu et al, 2021 ).…”

Section: Important Cells and Extracellular Matrix Involved In The Pat...mentioning

confidence: 99%

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

et al. 2022

Front. Pharmacol.

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Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease. Recent studies have identified the key role of crosstalk between dysregulated epithelial cells, mesenchymal, immune, and endothelial cells in IPF. In addition, genetic mutations and environmental factors (e.g., smoking) have also been associated with the development of IPF. With the recent development of sequencing technology, epigenetics, as an intermediate link between gene expression and environmental impacts, has also been reported to be implicated in pulmonary fibrosis. Although the etiology of IPF is unknown, many novel therapeutic targets and agents have emerged from clinical trials for IPF treatment in the past years, and the successful launch of pirfenidone and nintedanib has demonstrated the promising future of anti-IPF therapy. Therefore, we aimed to gain an in-depth understanding of the underlying molecular mechanisms and pathogenic factors of IPF, which would be helpful for the diagnosis of IPF, the development of anti-fibrotic drugs, and improving the prognosis of patients with IPF. In this study, we summarized the pathogenic mechanism, therapeutic targets and clinical trials from the perspective of multiple cell types, gene mutations, epigenetic and environmental factors.

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Section: Important Cells and Extracellular Matrix Involved In The Pat...mentioning

confidence: 99%

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

et al. 2022

Front. Pharmacol.

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“…In the treatment model, nintedanib, which was reported to target tyrosine kinases, was used as positive control to verify the inhibitory effect of BBJ on IPF ( Liu et al, 2021 ). Administrations of BBJ or NTB started from 7 days after building the lung fibrosis model and lasted 3 weeks, as displayed in Figure 6A .…”

Section: Resultsmentioning

confidence: 99%

Blueberry Juice Attenuates Pulmonary Fibrosis via Blocking the TGF-β1/Smad Signaling Pathway

Wang

Zhang

et al. 2022

Front. Pharmacol.

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Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal, and chronic lung disease, lacking a validated and effective therapy. Blueberry has demonstrated multiple pharmacological activities including anti-inflammatory, antioxidant, and anticancer. Therefore, the objective of this study was to investigate whether blueberry juice (BBJ) could ameliorate IPF. Experiments in vitro revealed that BBJ could significantly reduce the expressions of TGF-β1 modulated fibrotic protein, which were involved in the cascade of fibrosis in NIH/3T3 cells and human pulmonary fibroblasts. In addition, for rat primary lung fibroblasts (RPLFs), BBJ promoted the cell apoptosis along with reducing the expressions of α-SMA, vimentin, and collagen I, while increasing the E-cadherin level. Furthermore, BBJ could reverse epithelial–mesenchymal transition (EMT) phenotypic changes and inhibit cell migration, along with inducing the upregulation of E-cadherin in A549 cells. Compared with the vehicle group, BBJ treatment alleviated fibrotic pathological changes and collagen deposition in both bleomycin-induced prevention and treatment pulmonary fibrosis models. In fibrotic lung tissues, BBJ remarkably suppressed the expressions of collagen I, α-SMA, and vimentin and improved E-cadherin, which may be related to its inhibition of the TGF-β1/Smad pathway and anti-inflammation efficacy. Taken together, these findings comprehensively proved that BBJ could effectively prevent and attenuate idiopathic pulmonary fibrosis via suppressing EMT and the TGF-β1/Smad signaling pathway.

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“…These mediators encourage fibroblast proliferation, migration, and differentiation into myofibroblasts, which are immune to cell death and release collagens and other elements of the extracellular matrix (ECM). MMPs have been linked to the breakdown of ECM, which is controlled by a delicate balance between MMPs and tissue inhibitors of MMPs (TIMPs) according to earlier research [12][13][14][15][16][17][18] .…”

Section: Discussionmentioning

confidence: 99%

Relationship between disease severity and prognostic indicators and matrix metallaproteinase in patients with stable idiopatic pulmonary fibrosis

Baydar

Özyılmaz

Kont

et al. 2022

Cukurova Medical Journal

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Purpose: Blood-derived biomarkers have been extensively considered as possible prognostic indicators in idiopathic pulmonary fibrosis (IPF) recently. In order to assess the value of circulating biomarkers in common IPF clinical practice, the study intends to draw conclusions regarding the link between disease severity, prognostic indicators, and serum matrix metalloproteinase in patients with stable idiopathic pulmonary fibrosis. Materials and Methods: The study comprised 22 people with an IPF diagnosis that had been verified by a multidisciplinary approach. The sociodemographic details, clinical and radiologic symptoms, pulmonary function tests and the Gender-Age-Physiology (GAP) score were noted. ELISA has been used to research serum MMP concentrations. Results: There is no statistically significant correlation between the Matrix Metalloproteinase (MMP) 2, MMP 7, MMP 9, and MMP13 and the GAP index and, pulmonary function tests, or disease severity. GAP score was found to be higher in stage 3 in patients with severe disease, in stage 2 in patients with moderate disease, and in stage 1 in patients with mild disease. Conclusion: There are consistent findings in the literature, despite the fact that the association between MMP and IPF prognostic markers, pulmonary function tests, and disease severity could not be seen in this investigation. However, because they could open the door to a cutting-edge treatment strategy, these indicators should be investigated prospectively in larger series.

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A novel multikinase inhibitor SKLB‐YTH‐60 ameliorates inflammation and fibrosis in bleomycin‐induced lung fibrosis mouse models

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 17 publications

References 37 publications

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

Research Progress in the Molecular Mechanisms, Therapeutic Targets, and Drug Development of Idiopathic Pulmonary Fibrosis

Blueberry Juice Attenuates Pulmonary Fibrosis via Blocking the TGF-β1/Smad Signaling Pathway

Relationship between disease severity and prognostic indicators and matrix metallaproteinase in patients with stable idiopatic pulmonary fibrosis

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