Cytokine Production and Signaling in Stellate Cells

Marra, Fabio; Caligiuri, Alessandra

doi:10.1016/b978-0-12-800134-9.00005-1

Cited by 10 publications

(11 citation statements)

References 167 publications

(195 reference statements)

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“…For the wound closure test using a chamber migration assay, the influence of donor variability was demonstrated, where P2 promoted migration in donor 3 but suppressed this in donor 1 and 2. Nevertheless, the gene expression of OPN, which has been related to immune modulation and wound healing, 55 showed a similar pattern for the three donors, thus indicating that further studies are needed to confirm these findings. All these results indicate that both P2 and P6 are bioactive and that can maintain and promote the osteoblast phenotype more efficiently than EMD.…”

Section: Discussionmentioning

confidence: 71%

Xenohybrid Bone Graft Containing Intrinsically Disordered Proteins Shows Enhanced In Vitro Bone Formation

Zhu

Gómez

Xiao

et al. 2020

ACS Appl. Bio Mater.

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Bone defects are a significant health problem worldwide, as bone is the second-most transplanted tissue after blood. Although a myriad of bone grafts (BGs) have been used to treat bone repairs, none of them possesses all the desirable characteristics. An approach to improve BGs is to add bio-active components, however often difficult as BG production may disrupt the biological activities of such molecules. Here, we present a composite xenohybrid BG, SmartBonePep, with a type of biomolecule inspired by intrinsically disordered proteins (IDPs). These synthetic peptides (named P2 and P6) are physically entrapped into the polymer matrix of the composite BG. The effects of SmartBonePep on human osteoblasts were tested. Results showed that SmartBonePep enhanced proliferation and osteogenic effects. In order to verify the bioactivity of P2 and P6, these peptides were tested indirectly by being added to cell culture media too. Here, P2 or P6 exhibited promoting effects on osteogenic-related gene expressions. In this study, we showed highly effective osteoinductive synthetic peptides P2 or P6, which possess proline-rich and intrinsically disordered structural characters. This use of IDPs may provide promising bone enhancement biomolecules for clinical usage.

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Section: Discussionmentioning

confidence: 71%

Xenohybrid Bone Graft Containing Intrinsically Disordered Proteins Shows Enhanced In Vitro Bone Formation

Zhu

Gómez

Xiao

et al. 2020

ACS Appl. Bio Mater.

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“…6 Decreased expression of PPARγ, which inhibits Smad-3 expression, allows fibrogenesis to proceed. 6,7 IFNγ and TGFβ1 can stimulate expression of Smad-7 that inhibits Smad activity. 6 Os-teopontin, bFGF and CTGF are other cytokines that promote ECM synthesis by HSCs.…”

mentioning

confidence: 99%

“…6 Os-teopontin, bFGF and CTGF are other cytokines that promote ECM synthesis by HSCs. 3,6,7 Oxidative stress induced by various stimuli, including Ang II, in aHSCs also induces collagen I synthesis through the transcription factor p35C/EBP, which can be antagonized by TN-Fα-induced expression of p20C/EBP. 3,6,8 The JAK2 activation by Ang II also instigates RhoA/Rho-kinase (ROCK) pathway coupled to the migration and contraction of HSCs.…”

mentioning

confidence: 99%

Hepatic stellate cell activation and pro-fibrogenic signals

Gandhi

2017

Journal of Hepatology

113

117

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“…TGFβ characteristically promotes cellular activation (α-SMA) and increases extracellular matrix (ECM) deposition (including collagen type I and III and fibronectin), which is induced via intracellular Smad2/3 signaling [24]. TGFβ is also involved in the inhibition of matrix degradation, via suppression of matrix metalloproteinases (MMP1, 8, 13) and induction of tissue inhibitors of metalloproteinases (TIMP1, 2) and plasminogen activator inhibitor (PAI) [25]. PDGF-BB is the most potent growth factor essential in survival, proliferation and chemotaxis of HSCs via activation of Protein kinase B (PKB), also known as Akt, and extracellular signal-regulated kinase (ERK) 1/2 signaling [26].…”

Section: Discussionmentioning

confidence: 99%

Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis

et al. 2020

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The pivotal cell involved in the pathogenesis of liver fibrosis, i.e., the activated hepatic stellate cell (HSC), has a wide range of activities during the initiation, progression and even regression of the disease. These HSC-related activities encompass cellular activation, matrix synthesis and degradation, proliferation, contraction, chemotaxis and inflammatory signaling. When determining the in vitro and in vivo effectivity of novel antifibrotic therapies, the readout is currently mainly based on gene and protein levels of α-smooth muscle actin (α-SMA) and the fibrillar collagens (type I and III). We advocate for a more comprehensive approach in addition to these markers when screening potential antifibrotic drugs that interfere with HSCs. Therefore, we aimed to develop a gene panel for human in vitro and ex vivo drug screening models, addressing each of the HSC-activities with at least one gene, comprising, in total, 16 genes. We determined the gene expression in various human stellate cells, ranging from primary cells to cell lines with an HSC-origin, and human liver slices and stimulated them with two key profibrotic factors, i.e., transforming growth factor β (TGFβ) or platelet-derived growth factor BB (PDGF-BB). We demonstrated that freshly isolated HSCs showed the strongest and highest variety of responses to these profibrotic stimuli, in particular following PDGF-BB stimulation, while cell lines were limited in their responses. Moreover, we verified these gene expression profiles in human precision-cut liver slices and showed similarities with the TGFβ- and PDGF-BB-related fibrotic responses, as observed in the primary HSCs. With this study, we encourage researchers to get off the beaten track when testing antifibrotic compounds by including more HSC-related markers in their future work. This way, potential compounds will be screened more extensively, which might increase the likelihood of developing effective antifibrotic drugs.

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Cytokine Production and Signaling in Stellate Cells

Cited by 10 publications

References 167 publications

Xenohybrid Bone Graft Containing Intrinsically Disordered Proteins Shows Enhanced In Vitro Bone Formation

Xenohybrid Bone Graft Containing Intrinsically Disordered Proteins Shows Enhanced In Vitro Bone Formation

Hepatic stellate cell activation and pro-fibrogenic signals

Design of a Gene Panel to Expose the Versatile Role of Hepatic Stellate Cells in Human Liver Fibrosis

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