Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition

Mazza, Giuseppe; Telese, Andrea; Al‐Akkad, Walid; Frenguelli, Luca; Levi, Ana; Marrali, Martina; Longato, Lisa; Thanapirom, Kessarin; Vilia, Maria Giovanna; Lombardi, Benedetta; Crowley, Claire; Crawford, Mark; Karsdal, Morten A.; Leeming, Diana Julie; Marrone, Giusi; Böttcher, Katrin; Robinson, Benjamin; Hernández, Armando E. del Río; Tamburrino, Domenico; Spoletini, Gabriele; Malagó, Massimo; Hall, Andrew; Godovac‐Zimmermann, Jasminka; Luong, Tu Vinh; Coppi, Paolo De; Pinzani, Massimo; Rombouts, Krista

doi:10.3390/cells9010083

Cited by 51 publications

(57 citation statements)

References 39 publications

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“…Aetiology specific differences have also been observed. Mazza and colleagues report increased collagen 10A, 5A, fibulin 5, and fibronectin in cirrhotic liver from patients with HCC ( 31 ). Whereas, advanced ALD is associated with increased deposition of collagen type 1, upregulated synthesis of osteopontin (OPN) and increased synthesis of cellular fibronectin (cFN).…”

Section: Ecm In Chronic Liver Diseasementioning

confidence: 99%

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

et al. 2020

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Chronic liver disease when accompanied by underlying fibrosis, is characterized by an accumulation of extracellular matrix (ECM) proteins and chronic inflammation. Although traditionally considered as a passive and largely architectural structure, the ECM is now being recognized as a source of potent damage-associated molecular pattern (DAMP)s with immune-active peptides and domains. In parallel, the ECM anchors a range of cytokines, chemokines and growth factors, all of which are capable of modulating immune responses. A growing body of evidence shows that ECM proteins themselves are capable of modulating immunity either directly via ligation with immune cell receptors including integrins and TLRs, or indirectly through release of immunoactive molecules such as cytokines which are stored within the ECM structure. Notably, ECM deposition and remodeling during injury and fibrosis can result in release or formation of ECM-DAMPs within the tissue, which can promote local inflammatory immune response and chemotactic immune cell recruitment and inflammation. It is well described that the ECM and immune response are interlinked and mutually participate in driving fibrosis, although their precise interactions in the context of chronic liver disease are poorly understood. This review aims to describe the known pro-/anti-inflammatory and fibrogenic properties of ECM proteins and DAMPs, with particular reference to the immunomodulatory properties of the ECM in the context of chronic liver disease. Finally, we discuss the importance of developing novel biotechnological platforms based on decellularized ECM-scaffolds, which provide opportunities to directly explore liver ECM-immune cell interactions in greater detail.

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Section: Ecm In Chronic Liver Diseasementioning

confidence: 99%

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

et al. 2020

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“…The phosphorylated Smad2/3 proteins form a complex with common mediator Smad4 and then translocate into the nucleus to regulate TGF-β target gene expression [31][32][33]. Emerging evidence has proven that TGF-β signaling possesses both Smad and non-Smad pathways, and regulated tumorigenesis via different molecular mechanisms, including, TGF-β1/Smad2/3, PI3K-AKT-mTOR, Wnt, Notch, and ERK, p38, and JUN N-terminal kinase (JNK) MAPK pathways [34][35]. Various studies also indicated that TGF-β was signi cantly associated with the expression of MAGs and metabolic reprogramming of cancer [36][37][38].…”

Section: Discussionmentioning

confidence: 99%

Identification of metabolism-associated genes and construction of a prognostic signature in bladder cancer

Shen

Liu

Wang

et al. 2020

Preprint

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Background: Bladder cancer (BC) is a commonly diagnosed malignant tumor in the urinary system, with a high morbidity and recurrence rate. Current studies indicated that metabolism-associated genes (MAGs) having critical roles in the etiology of BC. The present study aims to identify differentially expressed MAGs and construct a MAGs based prognostic risk signature for BC by using The Cancer Genome Atlas (TCGA) database and proteomics data. Methods: RNA-sequence data from the TCGA database and proteomics data from our BC samples were used to identify differentially expressed MAGs and construct a MAGs based prognostic signature in BC. Subsequently, survival analysis and nomogram were used to evaluate the prognostic and predictive value of the MAGs based signature in BC. RNA isolation and reverse transcription‑quantitative PCR (RT-qPCR) was further perform to investigate the expression levels of MAGs in BC cells and explore the relationship between MAGs and M2 tumor associated macrophages (TAMs) secreted transforming growth factor-β1 (TGF-β1) in BC cells.Results: A total of 23 differentially expressed MAGs were identified and five MAGs were finally used to construct a MAGs based signature. Survival analysis revealed that the MAGs based signature was closely correlated with the survival outcomes of patients with BC. A nomogram with the MAGs based signature risk score and clinical features also constructed to facilitate the individualized prediction of BC patients. RT-qPCR showed that five MAGs were significantly differentially expressed and the expression levels of three MAGs were positively correlated with M2 TAM secreted TGF-β1 in T24 cells.Conclusions: Our study identified novel prognostic MAGs and constructed a MAGs based signature, which can be used as an independent factor in evaluating the prognosis of patients with BC. Furthermore, M2 TAMs may promote the expression of MAGs via the TGF-β1 signaling pathway in the microenvironment of BC. Further clinical trials and experimental exploration are needed to validate our observations in BC.

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“…56 Omics technologies such as proteomics or singlecell transcriptomics address issues with regards to characterisation of cells and matrices. [139][140][141][142] Novel non-destructive imaging techniques, such as micro-CT, optimal coherence tomography or 2photon microscopy promise to overcome the barrier of increased tissue thickness. [143][144][145] The use of second-harmonic generation or modified amino acids, such as azide-labelled proline, provides an ideal system for visualising matrix modifications.…”

Section: Challenges and Future Directionsmentioning

confidence: 99%

Tissue engineering of the biliary tract and modelling of cholestatic disorders

Brevini

Tysoe

Sampaziotis

2020

Journal of Hepatology

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Our insight into the pathogenesis of cholestatic liver disease remains limited, partly owing to challenges in capturing the multitude of factors that contribute to disease pathogenesis in vitro. Tissue engineering could address this challenge by combining cells, materials and fabrication strategies into dynamic modelling platforms, recapitulating the multifaceted aetiology of cholangiopathies. Herein, we review the advantages and limitations of platforms for bioengineering the biliary tree, looking at how these can be applied to model biliary disorders, as well as exploring future directions for the field.

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Cirrhotic Human Liver Extracellular Matrix 3D Scaffolds Promote Smad-Dependent TGF-β1 Epithelial Mesenchymal Transition

Cited by 51 publications

References 39 publications

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

Immunomodulatory Role of the Extracellular Matrix Within the Liver Disease Microenvironment

Identification of metabolism-associated genes and construction of a prognostic signature in bladder cancer

Tissue engineering of the biliary tract and modelling of cholestatic disorders

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