Profibrotic role of transcription factor SP1 in cross-talk between fibroblasts and M2 macrophages

Feng, Peng; Che, Ying; Gao, Chunyu; Chu, Xuelei; Li, Zhichao; Li, Luguang; Li, Jianguo; Gao, Jinghua; Dong, Yongli

doi:10.1016/j.isci.2023.108484

Cited by 3 publications

(1 citation statement)

References 41 publications

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“…Activated HSCs have also been reported to produce transforming growth factor-β1 (TGF-β1), which is known as a cytokine that induces fibrosis and acts in an autocrine manner 13 . TGF-β1 is produced by various types of cells, including M2-type macrophages as well as HSCs 14 . The production of cytokines such as TNF-α, IL-1, and TGF-β1 is promoted by signals downstream of DAMPs and PAMPs.…”

Section: Introductionmentioning

confidence: 99%

Assessing the combined impact of fatty liver-induced TGF-β1 and LPS-activated macrophages in fibrosis through a novel 3D serial section methodology

Ishiyama,

Hayatsu,

Toriumi

et al. 2024

Sci Rep

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Non-alcoholic steatohepatitis (NASH), caused by fat buildup, can lead to liver inflammation and damage. Elucidation of the spatial distribution of fibrotic tissue in the fatty liver in NASH can be immensely useful to understand its pathogenesis. Thus, we developed a novel serial section-3D (SS3D) technique that combines high-resolution image acquisition with 3D construction software, which enabled highly detailed analysis of the mouse liver and extraction and quantification of stained tissues. Moreover, we studied the underexplored mechanism of fibrosis progression in the fatty liver in NASH by subjecting the mice to a high-fat diet (HFD), followed by lipopolysaccharide (LPS) administration. The HFD/LPS (+) group showed extensive fibrosis compared with control; additionally, the area of these fibrotic regions in the HFD/LPS (+) group was almost double that of control using our SS3D technique. LPS administration led to an increase in Tnfα and Il1β mRNA expression and the number of macrophages in the liver. On the other hand, transforming growth factor-β1 (Tgfβ1) mRNA increased in HFD group compared to that of control group without LPS-administration. In addition, COL1A1 levels increased in hepatic stellate cell (HSC)-like XL-2 cells when treated with recombinant TGF-β1, which attenuated with recombinant latency-associated protein (rLAP). This attenuation was rescued with LPS-activated macrophages. Therefore, we demonstrated that fatty liver produced “latent-form” of TGF-β1, which activated by macrophages via inflammatory cytokines such as TNFα and IL1β, resulting in activation of HSCs leading to the production of COL1A1. Moreover, we established the effectiveness of our SS3D technique in creating 3D images of fibrotic tissue, which can be used to study other diseases as well.

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Section: Introductionmentioning

confidence: 99%

Assessing the combined impact of fatty liver-induced TGF-β1 and LPS-activated macrophages in fibrosis through a novel 3D serial section methodology

Ishiyama,

Hayatsu,

Toriumi

et al. 2024

Sci Rep

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Integrative analysis of transcriptome, DNA methylome, and chromatin accessibility reveals candidate therapeutic targets in hypertrophic cardiomyopathy

Gao,

Liu,

et al. 2024

Protein &Amp; Cell

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Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease and is characterized by primary left ventricular hypertrophy usually caused by mutations in sarcomere genes. The mechanism underlying cardiac remodeling in HCM remains incompletely understood. An investigation of HCM through integrative analysis at multi-omics levels will be helpful for treating HCM. DNA methylation and chromatin accessibility, as well as gene expression, were assessed by nucleosome occupancy and methylome sequencing (NOMe-seq) and RNA-seq, respectively, using the cardiac tissues of HCM patients. Compared with those of the controls, the transcriptome, DNA methylome and chromatin accessibility of the HCM myocardium showed multifaceted differences. At the transcriptome level, HCM hearts returned to the fetal gene program through decreased sarcomeric and metabolic gene expression and increased extracellular matrix gene expression. In the DNA methylome, hypermethylated and hypomethylated differentially methylated regions (DMRs) were identified in HCM. At the chromatin accessibility level, HCM hearts showed changes in different genome elements. Several transcription factors (TFs), including SP1 and EGR1, exhibited a fetal-like pattern of binding motifs in nucleosome-depleted regions (NDRs) in HCM. In particular, the inhibition of SP1 or EGR1 in an HCM mouse model harboring sarcomere mutations markedly alleviated the HCM phenotype of the mutant mice and reversed fetal gene reprogramming. Overall, this study not only provides a high precision multi-omics map of HCM heart tissue but also sheds light on the therapeutic strategy by intervening the fetal gene reprogramming in HCM.

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New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

Schmitz,

Alt,

Würfel

et al. 2024

Preprint

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BackgroundCurrent management options for partial tendon tears may not offer future potential to heal tissue and improve clinical results. This study tested the hypothesis that treatment of a partial rabbit common calcaneus tendon (CCT) defect with uncultured, autologous, adipose derived regenerative cells (UA-ADRCs) enables regenerative healing without scar formation, as recently observed in a biopsy of a human supraspinatus tendon.MethodsA full-thickness hole (diameter, 3 mm) was punched into the midsubstance of the right gastrocnemius tendon (GT; which is a part of the CCT) of adult, female New Zealand white rabbits. Immediately thereafter the rabbits were treated by application of an averaged 28.3×106UA-ADRCs in 0.5 ml lactated Ringer’s solution (RLS) into the GT defect and surrounding tendon tissue, or underwent sham treatment. Rabbits were sacrificed either four weeks (W4) or twelve weeks (W12) post-treatment, and the CCTs were investigated using histology, immunohistochemistry and non-destructive biomechanical testing.ResultsNewly formed connective tissue was consistent with the formation of new tendon tissue after treatment with UA-ADRCs, and with the formation of scar tissue after sham treatment, at both W4 and W12 post-treatment. Biomechanical testing demonstrated a significantly higher mean percent relaxation after treatment with UA-ADRCs than after sham treatment (p < 0.05), and significant, negative correlations between the peak stress as well as the equilibrium stress and the cross-sectional area of the CCT (p < 0.05) after treatment with UA-ADRCs but not after sham treatment.ConclusionsManagement of partial tendon tears with UA-ADRCs has the potential to be truly “structure-modifying”.

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Profibrotic role of transcription factor SP1 in cross-talk between fibroblasts and M2 macrophages

Cited by 3 publications

References 41 publications

Assessing the combined impact of fatty liver-induced TGF-β1 and LPS-activated macrophages in fibrosis through a novel 3D serial section methodology

Assessing the combined impact of fatty liver-induced TGF-β1 and LPS-activated macrophages in fibrosis through a novel 3D serial section methodology

Integrative analysis of transcriptome, DNA methylome, and chromatin accessibility reveals candidate therapeutic targets in hypertrophic cardiomyopathy

New, biomechanically sound tendon tissue after injection of uncultured, autologous, adipose derived regenerative cells in partial Achilles tendon defects in rabbits

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