Bone morphogenetic protein 7 attenuates epithelial–mesenchymal transition induced by silica

2015 ◽  
Vol 35 (1) ◽  
pp. 69-77 ◽  
Author(s):  
G Yang ◽  
Z Zhu ◽  
Y Wang ◽  
A Gao ◽  
P Niu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Bone Morphogenetic Protein ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Bone Morphogenetic Protein 7 ◽  
Mesenchymal Transition ◽  
Morphogenetic Protein ◽  
Epithelial Marker

The epithelial–mesenchymal transition (EMT) is a critical process in the pulmonary fibrosis. It has been reported that bone morphogenetic protein 7 (BMP-7) was able to reverse EMT in proximal tubular cells. Therefore, we test the hypothesis that EMT contributes to silica-induced pulmonary fibrosis and BMP-7 inhibits EMT in silica-induced pulmonary fibrosis. Progressive silica-induced pulmonary fibrosis in the rat was used as a model of silicosis. Epithelial and mesenchymal markers were measured from rat fibrotic lungs. Then the effects of BMP-7 on the EMT were further confirmed in A549 cells. There are increases of vimentin as a mesenchymal marker and decreases of E-cadherin as an epithelial marker in the silica-exposed rat lungs, which is in agreement with the A549 cells data. However, BMP-7 treatment significantly reduced expression of vimentin in the rat pulmonary fibrosis model and in A549 cells. In conclusion, EMT contributes to silica-induced pulmonary fibrosis. Meanwhile, the treatment of BMP-7 can inhibit silica-induced EMT in vitro and in vivo.

scholarly journals Bone morphogenetic protein-7 prevented epithelial-mesenchymal transition in RLE-6TN cells

2016 ◽  
Vol 5 (3) ◽  
pp. 931-937 ◽  
Author(s):  
Yan Wang ◽  
Di Liang ◽  
Zhonghui Zhu ◽  
Xiaoli Li ◽  
Guoliang An ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Epithelial Mesenchymal Transition ◽  
Bone Morphogenetic Protein 7 ◽  
Mesenchymal Transition ◽  
Morphogenetic Protein

Silica induced EMT and decreased the expression of BMP-7 in vivo and in vitro, while exogenous BMP-7 promoted MET and inhibited silica-induced EMT associated with inhibition of the p38 MAPK/transcription factor (TF) signaling pathway in RLE-6TN cells.

scholarly journals Arctigenin Suppressed Epithelial-Mesenchymal Transition Through Wnt3a/β-Catenin Pathway in PQ-Induced Pulmonary Fibrosis

2020 ◽  
Vol 11 ◽  
Author(s):  
Fei Gao ◽  
Yun Zhang ◽  
Zhizhou Yang ◽  
Mengmeng Wang ◽  
Zhiyi Zhou ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Lung Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Alveolar Type ◽  
Mesenchymal Transition

Arctigenin (ATG), a major bioactive substance of Fructus Arctii, counters renal fibrosis; however, whether it protects against paraquat (PQ)-induced lung fibrosis remains unknown. The present study was to determine the effect of ATG on PQ-induced lung fibrosis in a mouse model and the underlying mechanism. Firstly, we found that ATG suppressed PQ-induced pulmonary fibrosis by blocking the epithelial-mesenchymal transition (EMT). ATG reduced the expressions of Vimentin and α-SMA (lung fibrosis markers) induced by PQ and restored the expressions of E-cadherin and Occludin (two epithelial markers) in vivo and in vitro. Besides, the Wnt3a/β-catenin signaling pathway was significantly activated in PQ induced pulmonary fibrosis. Further analysis showed that pretreatment of ATG profoundly abrogated PQ-induced EMT-like phenotypes and behaviors in A549 cells. The Wnt3a/β-catenin signaling pathway was repressed by ATG treatment. The overexpression of Wnt3a could weaken the therapeutic effect of ATG in A549 cells. These findings suggested that ATG could serve as a new therapeutic candidate to inhibit or even reverse EMT-like changes in alveolar type II cells during PQ-induced lung fibrosis, and unraveled that the Wnt3a/β-catenin pathway might be a mechanistic tool for ATG to control pulmonary fibrosis.

Galangin ameliorated pulmonary fibrosis in vivo and in vitro by regulating epithelial-mesenchymal transition

2020 ◽  
Vol 28 (19) ◽  
pp. 115663
Author(s):  
Liqun Wang ◽  
Hongyao Liu ◽  
Qiurong He ◽  
Cailing Gan ◽  
Yali Li ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals Irradiation Activates MZF1 to Inhibit miR-541-5p Expression and Promote Epithelial-Mesenchymal Transition (EMT) in Radiation-Induced Pulmonary Fibrosis (RIPF) by Upregulating Slug

2021 ◽  
Vol 22 (21) ◽  
pp. 11309
Author(s):  
Xinxin Liang ◽  
Ziyan Yan ◽  
Ping Wang ◽  
Yuhao Liu ◽  
Xingkun Ao ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Targets ◽  
Alveolar Epithelial Cells ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Radiation Induced ◽  
Myeloid Zinc Finger

Understanding miRNAs regulatory roles in epithelial-mesenchymal transition (EMT) would help establish new avenues for further uncovering the mechanisms underlying radiation-induced pulmonary fibrosis (RIPF) and identifying preventative and therapeutic targets. Here, we demonstrated that miR-541-5p repression by Myeloid Zinc Finger 1 (MZF1) promotes radiation-induced EMT and RIPF. Irradiation could decrease miR-541-5p expression in vitro and in vivo and inversely correlated to RIPF development. Ectopic miR-541-5p expression suppressed radiation-induced-EMT in vitro and in vivo. Knockdown of Slug, the functional target of miR-541-5p, inhibited EMT induction by irradiation. The upregulation of transcription factor MZF1 upon irradiation inhibited the expression of endogenous miR-541-5p and its primary precursor (pri-miR-541-5p), which regulated the effect of the Slug on the EMT process. Our finding showed that ectopic miR-541-5p expression mitigated RIPF in mice by targeting Slug. Thus, irradiation activates MZF1 to downregulate miR-541-5p in alveolar epithelial cells, promoting EMT and contributing to RIPF by targeting Slug. Our observation provides further understanding of the development of RIPF and determines potential preventative and therapeutic targets.

scholarly journals Bleomycin induces epithelial-to-mesenchymal transition via bFGF/PI3K/ESRP1 signaling in pulmonary fibrosis

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Chang-Mei Weng ◽  
Qing Li ◽  
Kui-Jun Chen ◽  
Cheng-Xiong Xu ◽  
Meng-Sheng Deng ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Regulatory Protein ◽  
A549 Cells ◽  
Akt Signaling ◽  
High Rate ◽  
Akt Inhibitor ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Idiopathic pulmonary fibrosis (IPF) is a fatal and chronic disease with a high rate of infection and mortality; however, its etiology and pathogenesis remain unclear. Studies have revealed that epithelial–mesenchymal transition (EMT) is a crucial cellular event in IPF. Here, we identified that the pulmonary fibrosis inducer bleomycin simultaneously increased the expression of bFGF and TGF-β1 and inhibited epithelial-specific regulatory protein (ESRP1) expression in vivo and in vitro. In addition, in vitro experiments showed that bFGF and TGF-β1 down-regulated the expression of ESRP1 and that silencing ESRP1 promoted EMT in A549 cells. Notably, we determined that bFGF activates PI3K/Akt signaling, and treatment with the PI3K/Akt inhibitor LY294002 inhibited bleomycin-induced cell morphology changes and EMT. In addition, the effects of LY294002 on bleomycin-induced EMT were inhibited by ESRP1 silencing in A549 cells. Taken together, these findings suggest that bleomycin induced EMT through down-regulating ESRP1 by simultaneously increasing bFGF and TGF-β1 in pulmonary fibrosis. Additionally, our findings indicated that bFGF inhibits ESRP1 by activating PI3K/Akt signaling.

scholarly journals Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Ling Peng ◽  
Li Wen ◽  
Qing-Feng Shi ◽  
Feng Gao ◽  
Bin Huang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Matrix Metalloproteinase 2 ◽  
Mesenchymal Transition ◽  
The Impact ◽  
Anti Inflammation ◽  
Iκbα Degradation

AbstractIdiopathic pulmonary fibrosis (IPF) is featured with inflammation and extensive lung remodeling caused by overloaded deposition of extracellular matrix. Scutellarin is the major effective ingredient of breviscapine and its anti-inflammation efficacy has been reported before. Nevertheless, the impact of scutellarin on IPF and the downstream molecular mechanism remain unclear. In this study, scutellarin suppressed BLM-induced inflammation via NF-κB/NLRP3 pathway both in vivo and in vitro. BLM significantly elevated p-p65/p65 ratio, IκBα degradation, and levels of NLRP3, caspase-1, caspase-11, ASC, GSDMDNterm, IL-1β, and IL-18, while scutellarin reversed the above alterations except for that of caspase-11. Scutellarin inhibited BLM-induced epithelial–mesenchymal transition (EMT) process in vivo and in vitro. The expression levels of EMT-related markers, including fibronectin, vimentin, N-cadherin, matrix metalloproteinase 2 (MMP-2) and MMP-9, were increased in BLM group, and suppressed by scutellarin. The expression level of E-cadherin showed the opposite changes. However, overexpression of NLRP3 eliminated the anti-inflammation and anti-EMT functions of scutellarin in vitro. In conclusion, scutellarin suppressed inflammation and EMT in BLM-induced pulmonary fibrosis through NF-κB/NLRP3 signaling.

Effect and Mechanism of Qingfei Paidu Decoction in the Management of Pulmonary Fibrosis and COVID-19

2021 ◽  
pp. 1-19
Author(s):  
Yu Wu ◽  
Lili Xu ◽  
Gang Cao ◽  
Lingtian Min ◽  
Tingting Dong
Keyword(s):  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Network Pharmacology ◽  
Mesenchymal Transition ◽  
Antifibrotic Therapy ◽  
M2 Polarization ◽  
Key Factor ◽  
Novel Coronavirus

Qingfei Paidu decoction (QFPD) has been repeatedly recommended for the clinical treatment of novel coronavirus disease 2019 (COVID-19) in multiple provinces throughout China. A possible complication of COVID-19 lung involvement is pulmonary fibrosis, which causes chronic breathing difficulties and affects the patient’s quality of life. Therefore, there is an important question regarding whether QFPD can alleviate the process of pulmonary fibrosis and its potential mechanisms. To explore this issue, this study demonstrated the anti-pulmonary fibrosis activity and mode of action of QFPD in vivo and in vitro pulmonary fibrosis models and network pharmacology. The results showed that QFPD effectively ameliorated the bleomycin-induced inflammation and collagen deposition in mice and significantly improved the epithelial-mesenchymal transition in pulmonary fibrosis in mice. In addition, QFPD inhibited bleomycin-induced M2 polarization of macrophages in pulmonary tissues. An in-depth study of the mechanism of QFPD in the treatment of pulmonary fibrosis based on network pharmacology and molecular simulation revealed that SRC was the main target of QFPD and sitosterol (a key compound in QFPD). QFPD and sitosterol regulate the EMT process and M2 polarization of macrophages by inhibiting the activation of SRC, thereby alleviating pulmonary fibrosis in mice. COVID-19 infection might produce severe fibrosis, and antifibrotic therapy with QFPD may be valuable in preventing severe neocoronavirus disease in patients with IPF, which could be a key factor explaining the role of QFPD in the treatment of COVID-19.

scholarly journals Emodin Ameliorates High Glucose Induced-Podocyte Epithelial-Mesenchymal Transition In-Vitro and In-Vivo

2015 ◽  
Vol 35 (4) ◽  
pp. 1425-1436 ◽  
Author(s):  
Tingfang Chen ◽  
Li Yang Zheng ◽  
Wenzhen Xiao ◽  
Dingkun Gui ◽  
Xiaoxia Wang ◽  
...  
Keyword(s):  
High Glucose ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Option ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Mesenchymal Transition ◽  
Epithelial Marker

Background: Epithelial-to-mesenchymal transition (EMT) is a potential pathway leading to podocyte depletion and proteinuria in diabetic kidney disease (DKD). Here, we investigated the protective effects of Emodin (EMO) on high glucose (HG) induced-podocyte EMT in-vitro and in-vivo. Methods: Conditionally immortalized mouse podocytes were exposed to HG with 30μg /ml of EMO and 1μmol/ml of integrin-linked kinase (ILK) inhibitor QLT0267 for 24 h. Streptozotocin (STZ)-induced diabetic rats were treated with EMO at 20 mg· kg-1· d-1 and QLT0267 at 10 mg· kg-1· w-1 p.o., for 12 weeks. Albuminuria and blood glucose level were measured. Immunohistochemistry, immunofluorescence, western blotting and real-time PCR were used to detect expression of ILK, the epithelial marker of nephrin and the mesenchymal marker of desmin in-vitro and in-vivo. Results: HG increased podocyte ILK and desmin expression while decreased nephrin expression. However, EMO significantly inhibited ILK and desmin expression and partially restored nephrin expression in HG-stimulated podocytes. These in-vitro observations were further confirmed in-vivo. Treatment with EMO for 12 weeks attenuated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. EMO also repressed renal ILK and desmin expression, preserved nephrin expression, as well as ameliorated albuminuria in STZ-induced diabetic rats. Conclusion: EMO ameliorated glucose-induced EMT and subsequent podocyte dysfunction partly through ILK and desmin inhibition as well as nephrin upregulatiotion, which might provide a potential novel therapeutic option for DKD.

scholarly journals Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation

2013 ◽  
Vol 210 (12) ◽  
pp. 2597-2610 ◽  
Author(s):  
Nighat Yasmin ◽  
Thomas Bauer ◽  
Madhura Modak ◽  
Karin Wagner ◽  
Christopher Schuster ◽  
...  
Keyword(s):  
Bone Morphogenetic Protein ◽  
Prenatal Development ◽  
Langerhans Cell ◽  
Type I ◽  
Blood Monocytes ◽  
Bone Morphogenetic Protein 7 ◽  
Morphogenetic Protein ◽  
Tgf Β1

Human Langerhans cell (LC) precursors populate the epidermis early during prenatal development and thereafter undergo massive proliferation. The prototypic antiproliferative cytokine TGF-β1 is required for LC differentiation from human CD34+ hematopoietic progenitor cells and blood monocytes in vitro. Similarly, TGF-β1 deficiency results in LC loss in vivo. However, immunohistology studies revealed that human LC niches in early prenatal epidermis and adult basal (germinal) keratinocyte layers lack detectable TGF-β1. Here we demonstrated that these LC niches express high levels of bone morphogenetic protein 7 (BMP7) and that Bmp7-deficient mice exhibit substantially diminished LC numbers, with the remaining cells appearing less dendritic. BMP7 induces LC differentiation and proliferation by activating the BMP type-I receptor ALK3 in the absence of canonical TGF-β1–ALK5 signaling. Conversely, TGF-β1–induced in vitro LC differentiation is mediated via ALK3; however, co-induction of ALK5 diminished TGF-β1–driven LC generation. Therefore, selective ALK3 signaling by BMP7 promotes high LC yields. Within epidermis, BMP7 shows an inverse expression pattern relative to TGF-β1, the latter induced in suprabasal layers and up-regulated in outer layers. We observed that TGF-β1 inhibits microbial activation of BMP7-generated LCs. Therefore, TGF-β1 in suprabasal/outer epidermal layers might inhibit LC activation, resulting in LC network maintenance.

Sign in / Sign up

Export Citation Format

Share Document