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Follistatin-like 1 guarantees the immunomodulatory properties of mesenchymal stem cells during liver fibrotic therapy

ABSTRACT: Follistatin-like 1 guarantees the immunomodulatory properties of mesenchymal stem cells during liver fibrotic therapy

PROVIDER: PRJNA835460 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19100229_1.fastq.gz	Fastqsanger.gz
	SRR19100229_2.fastq.gz	Fastqsanger.gz
	SRR19100230_1.fastq.gz	Fastqsanger.gz
	SRR19100230_2.fastq.gz	Fastqsanger.gz
	SRR19100231_1.fastq.gz	Fastqsanger.gz

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Follistatin-like 1 guarantees the immunomodulatory properties of mesenchymal stem cells during liver fibrotic therapy

Project description:Mesenchymal stem cell (MSC) therapy has been shown to be a promising option for liver fibrosis treatment. However, critical factors affecting the efficacy of MSC therapy for liver fibrosis remain unknown. Follistatin-like 1 (FSTL1), a TGF--induced matricellular protein, is documented as an intrinsic regulator of proliferation and differentiation in MSCs. In the present study, we characterized the potential role of FSTL1 in MSC-based anti-fibrotic therapy and further elucidated the mechanisms underlying its action. Human umbilical cord-derived MSCs were characterized by flow cytometry. FSTL1low MSCs was achieved by FSTL1 siRNA. Migration capacity was evaluated by wound-healing and transwell assay. A murine liver fibrotic model was created by carbon tetrachloride (CCl4) injection, while control MSCs or FSTL1low MSC were transplanted via intravenous injection 12 weeks post CCl4 injection. Histopathology, liver function, fibrosis degree, and inflammation were analysed thereafter. Inflammatory cell infiltration was evaluated by flow cytometry after hepatic nonparenchymal cell isolation. An MSC-macrophage co-culture system was constructed to further confirm the role of FSTL1 in the immunosuppressive capacity of MSCs. RNA sequencing was used to screen target genes of FSTL1. FSTL1low MSCs had comparable gene expression for surface markers to wildtype but limited differentiation and migration capacity. FSTL1low MSCs failed to alleviate CCl4-induced hepatic fibrosis in a mouse model. Our data indicated that FSTL1 is essential for the immunosuppressive action of MSCs on inflammatory macrophages during liver fibrotic therapy. FSTL1 silencing attenuated this capacity by inhibiting the downstream JAK/STAT1/IDO pathway. Our data suggest that FSTL1 facilitates the immunosuppression of MSCs on macrophages and that guarantee the anti-fibrotic effect of MSCs in liver fibrosis.

2024-04-30 | GSE202320 | GEO

Endogenous Follistatin-like 1 guarantees the immunomodulatory properties of mesenchymal stem cells during liver fibrotic therapy.

Project description:Mesenchymal stem cell (MSC) therapy has been shown to be a promising option for liver fibrosis treatment. However, critical factors affecting the efficacy of MSC therapy for liver fibrosis remain unknown. Follistatin-like 1 (FSTL1), a TGF-β-induced matricellular protein, is documented as an intrinsic regulator of proliferation and differentiation in MSCs. In the present study, we characterized the potential role of FSTL1 in MSC-based anti-fibrotic therapy and further elucidated the mechanisms underlying its action. Human umbilical cord-derived MSCs were characterized by flow cytometry. FSTL1low MSCs were achieved by FSTL1 siRNA. Migration capacity was evaluated by wound-healing and transwell assay. A murine liver fibrotic model was created by carbon tetrachloride (CCl4) injection, while control MSCs or FSTL1low MSC were transplanted via intravenous injection 12 weeks post CCl4 injection. Histopathology, liver function, fibrosis degree, and inflammation were analysed thereafter. Inflammatory cell infiltration was evaluated by flow cytometry after hepatic nonparenchymal cell isolation. An MSC-macrophage co-culture system was constructed to further confirm the role of FSTL1 in the immunosuppressive capacity of MSCs. RNA sequencing was used to screen target genes of FSTL1. FSTL1low MSCs had comparable gene expression for surface markers to wildtype but limited differentiation and migration capacity. FSTL1low MSCs failed to alleviate CCl4-induced hepatic fibrosis in a mouse model. Our data indicated that FSTL1 is essential for the immunosuppressive action of MSCs on inflammatory macrophages during liver fibrotic therapy. FSTL1 silencing attenuated this capacity by inhibiting the downstream JAK/STAT1/IDO pathway. Our data suggest that FSTL1 facilitates the immunosuppression of MSCs on macrophages and that guarantee the anti-fibrotic effect of MSCs in liver fibrosis.

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YAP/TAZ regulates immunomodulatory properties of mesenchymal stem cells

Project description:YAP/TAZ regulates immunomodulatory properties of mesenchymal stem cells

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Expansion of human bone marrow-derived mesenchymal stromal cells with enhanced immunomodulatory properties

Project description:Expansion of human bone marrow-derived mesenchymal stromal cells with enhanced immunomodulatory properties

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Immunomodulatory properties of slowly cycling and mesenchymal-like castration-resistant prostate cancer stem cells

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Remdesivir has previously unknown anti-viral immunomodulatory properties through the Adenosine A2A Receptor pathway

Project description:The COVID-19 pandemic has unveiled an urgent need for new anti-virals to control emerging infectious diseases and potential future pandemics. Classic anti-virals are currently designed to directly interfere with pathogens. However, anti-virals are often insufficient to rapidly clear infections in the absence of an effective immune response. Immunotherapy could complement the use of anti-virals, however its application to infectious diseases remains largely unexplored. In this work, we found that the anti-viral drug remdesivir has previously unknown immunomodulatory properties which contribute to its therapeutic effect against SARS-CoV-2. These properties are due to remdesivir metabolite, GS-441524, acting as an Adenosine A2A Receptor antagonist, a function that is distinct from its intrinsic anti-viral activity. Our findings support a new rationale for the design of next-generation anti-viral agents with dual – immunomodulatory and intrinsic - anti-viral properties. These compounds could represent game-changing therapies to control emerging viral diseases and future pandemics.

2024-09-11 | GSE236563 | GEO

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Project description:Human adipose mesenchymal stem cells are a heterogeneous population, where cell cultures derived from single cell-expanded clones present varying degrees of differential plasticity. This work focuses on the immunomodulatory/anti-inflammatory properties of these cells. To this end, 5 single cell clones were isolated (1.X and 3.X) from 2 volunteers. Regarding the expression level of the lineage-characteristic surface antigens, clones 1.10 and 1.22 expressed the lowest amounts, while clones 3.10 and 3.5 expressed more CD105 than the rest and clone 1.7 expressed higher amounts of CD73 and CD44. Regarding cytokine secretion, all clones were capable of spontaneously releasing high levels of IL-6 and low to moderate levels of IL-8. Furthermore, clone 3.X produced the highest amounts of pro-inflammatory cytokines such as IL-1β, while clones 1.10 and 1.22 highly expressed IL-4 and IL-5. These differences can be explained in part by the distinct DNA promoter methylation profile exhibited by the clones. The results of this work indicates that this stem cell population is heterogeneous in its secretion profile, and that isolation, characterization and selection of the appropriate cell clone is a more exact method for the possible treatment of different patients or pathologies. Total DNA isolated by standard procedures from different clones of human dipose mesenchymal stem cells (hMSC)

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Changes in follistatin levels by BRCA1 may serve as a regulator of ovarian carcinogenesis

Project description:Follistatin is a folliculogenesis regulating protein that has been found in relatively high concentration in the female ovarian tissues. Follistatin acts as an antagonist to the function of Activin, which is often found elevated in ovarian carcinogenesis and thus presents a possibility for therapeutic intervention in controlling ovarian cancer. Most of the ovarian cancer occurs in its ovarian surface epithelium (OSE) cells. Although breast cancer susceptibility gene 1 (BRCA1) is a known tumor suppressor for breast cancer but its role in ovarian cancer is beginning to unfold. We have shown that in ovarian carcinoma cells (SKOV3), stable overexpression of BRCA1 stimulates Follistatin secretion and simultaneously downregulates Activin expression. Moreover, knock down of BRCA1 in immortalized OSE (IOSE) cells from human ovarian tissue demonstrates downregulation of Follistatin secretion with simultaneous up regulation of Activin expression. IOSE cells generated from an ovarian cancer patient with BRCA1 mutation failed to secrete Follistatin in the medium. Our results indicate a novel function for BRCA1 in the form of regulation of the expression of Follistatin in the ovarian cells.

2011-07-02 | GSE30296 | GEO

Remdesivir has previously unknown anti-viral immunomodulatory properties through the Adenosine A2A Receptor pathway

Project description:Remdesivir has previously unknown anti-viral immunomodulatory properties through the Adenosine A2A Receptor pathway

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Loss of immunosuppressive and anti-inflammatory properties in transformed human mesenchymal stem cells

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2015-05-14 | GSE55108 | GEO

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