Milk Fat Globule EGF and Factor V/VIII Domain Containing (MFGE8) as a Novel Player in Equine Endometrial Fibrosis
Ontology highlight
ABSTRACT:
ORGANISM(S): Equus caballus
PROVIDER: GSE302877 | GEO | 2026/03/25
REPOSITORIES: GEO
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Project description:White adipose tissue (WAT) fibrosis is a major determinant of obesity-induced cardiometabolic dysfunction and is characterized by excessive extracellular matrix (ECM) deposition and myofibroblast activation. Transforming growth factor (TGF)-β1 is a profibrotic cytokine that potently induces myofibroblast activation in adipocyte stem cells (ASC). How TGF-β1 orchestrates ASC activation in WAT fibrosis is not completely understood. We identified FOXS1, a member of the forkhead box transcription factor superfamily, as a transcriptional target of TGF-β1 signaling in primary human WAT ASC (hASC). FOXS1 potentiated TGF-β1-dependent upregulation of several myofibroblast genes (e.g. Acta2, Col1a1, Fn1, Il11) in 10T1/2 fibroblasts. FOXS1 also mitigated the induction of several adipogenic factors (e.g. Pparg, Stat5a, Fabp4, Adipoq) in 10T1/2 fibroblasts and sensitized these cells to the anti-adipogenic effects of TGF-β1. Furthermore, loss of endogenous FOXS1 improved adipogenic permissiveness and activated proadipogenic gene programs in 10T1/2 cells, even after TGF-β1 stimulation. These results indicate that FOXS1 is a positive regulator of profibrotic TGF-β1-dependent cellular responses, orchestrating the regulation of molecular phenotypes that promote myofibroblast activation and block adipogenesis. These findings offer novel insight into the TGF-β1-dependent roles of FOXS1 in fibroblasts within the context of profibrotic ASC activation and provide a foundation for further investigation into the role of FOXS1 in WAT fibrosis and obesity-induced cardiometabolic dysfunction.
2025-08-01 | GSE302341 | GEO
Project description:White adipose tissue (WAT) fibrosis is a major determinant of obesity-induced cardiometabolic dysfunction and is characterized by excessive extracellular matrix (ECM) deposition and myofibroblast activation. Transforming growth factor (TGF)-β1 is a profibrotic cytokine that potently induces myofibroblast activation in adipocyte stem cells (ASC). How TGF-β1 orchestrates ASC activation in WAT fibrosis is not completely understood. We identified FOXS1, a member of the forkhead box transcription factor superfamily, as a transcriptional target of TGF-β1 signaling in primary human WAT ASC (hASC). FOXS1 potentiated TGF-β1-dependent upregulation of several myofibroblast genes (e.g. Acta2, Col1a1, Fn1, Il11) in 10T1/2 fibroblasts. FOXS1 also mitigated the induction of several adipogenic factors (e.g. Pparg, Stat5a, Fabp4, Adipoq) in 10T1/2 fibroblasts and sensitized these cells to the anti-adipogenic effects of TGF-β1. Furthermore, loss of endogenous FOXS1 improved adipogenic permissiveness and activated proadipogenic gene programs in 10T1/2 cells, even after TGF-β1 stimulation. These results indicate that FOXS1 is a positive regulator of profibrotic TGF-β1-dependent cellular responses, orchestrating the regulation of molecular phenotypes that promote myofibroblast activation and block adipogenesis. These findings offer novel insight into the TGF-β1-dependent roles of FOXS1 in fibroblasts within the context of profibrotic ASC activation and provide a foundation for further investigation into the role of FOXS1 in WAT fibrosis and obesity-induced cardiometabolic dysfunction.
2025-08-01 | GSE302340 | GEO
Project description:Primary cardiac fibroblasts were isolated from neonatal C57BL/6J mouse hearts and stimulated with TGF-β1 in vitro to induce a profibrotic phenotype. Bulk RNA sequencing was performed on fibroblasts treated with TGF-β for 48 hours and on matched untreated controls to characterize transcriptional programs associated with TGF-β–driven fibroblast activation. Differential expression and gene ontology analyses were used to identify pathways related to extracellular matrix remodeling, TGF-β signaling, and DNA damage responses. These data support mechanistic studies on CRABP2–MRE11–MRN–dependent regulation of cardiac fibroblast activation and fibrosis.
2026-01-06 | GSE315365 | GEO
Project description:Fibrotic diseases have significant health impact and have been associated with differentiation of the resident fibroblasts into myofibroblasts. In particular, stiffened extracellular matrix and TGF-β1 in fibrotic lesions have been shown to promote pathogenic myofibroblast activation and progression of fibrosis in various tissues. To better understand the roles of mechanical and chemical cues on myofibroblast differentiation and how they may crosstalk, we cultured primary valvular interstitial cells (VICs) isolated from porcine aortic valves and studied how traditional TCPS culture, which presents a non-physiologically stiff environment, and TGF-β1 affect native VIC phenotypes. We carried out gene expression profiling using porcine genome microarrays from Affymetrix and found that traditional TCPS culture induces major changes in gene expression of native VICs, rendering these cells more activated and similar to cells treated with TGF-β1. We also monitored time-dependent effects induced by TGF-β1 by examining gene expression changes induced by TGF-β1 at 8 hours and 24 hours. Porcine aortic VICs were isolated and cultured with or without TGF-β1 treatment for RNA extraction and hybridization on Affymetrix microarrays. We included 3 biological replicates for each condition. P0 VICs were freshly isolated cells which had not been cultured. P2 VICs were cells that had been passaged 2 times and cultured on plastic plates in low serum media. Some of the P2 VICs were treated with TGF-β1 at 5ng/ml for 8 hours or 24 hours. All the control and TGF-β1-treated conditions were collected at the same time on day 3 of culture.
2013-09-02 | E-GEOD-48839 | biostudies-arrayexpress
Project description:To elucidate how TGF-β1 regulates translation, we treated human lung fibroblasts (HLF) with TGF-β1 and used RNA-seq to determine the effect of TGF-β1 on total RNAs, and mRNA polysome/monosome ratios.
2022-04-28 | GSE201506 | GEO
Project description:We aimed to identify miRNA biomarkers of renal injury in kidney biopsies from patients with lupus nephritis. MiRNA profiles of 8 patients were analyzed for correlation with various clinical features including Progression, Activity, Chronicity, and Time to Kidney Failure. MicroRNAs (miRs) are promising biomarkers and are involved in pathogenesis of kidney diseases. We aimed to identify miR biomarkers of renal injury in kidney biopsies from patients with lupus nephritis and study their potential role in renal fibrosis. miR-150 was significantly increased in kidneys with high chronicity compared to low chronicity and it correlated positively with chronicity index scores and renal collagen I expression. In kidneys with high chronicity, miR-150 was found predominantly in proximal tubular cells (PTCs) and was moderately expressed in podocytes and to lesser degree in mesangial cells (MCs). We hypothesized that miR-150 increases fibrosis by downregulating a negative regulator of profibrotic proteins. Suppressor of cytokine signaling1 (SOCS1) is a predicted target of miR-150 and has shown antifibrotic role. After confirming that SOCS1 is a direct target of miR-150, we showed that transfection of a miR-150 analog downregulated SOCS1 protein and upregulated the profibrotic proteins fibronectin, collagen I, collagen III, and TGF-β1 in both primary normal human renal PTCs and MCs. A similar effect was seen when using a SOCS1 siRNA to confirm that the effect of miR-150 on profibrotic proteins is mediated through SOCS1. Stimulation with TGF-β1 induced miR-150 increase in PTCs and human podocytes but not MCs. These results suggest that miR-150 might be a useful quantitative renal biomarker of kidney injury in lupus nephritis and that miR-150, which might be partially induced by TGF-β1, plays an important role in renal fibrosis by increasing profibrotic molecules through downregulation of SOCS1. FFPE kidney specimens (n=25) including baseline and repeated needle renal biopsies were from 14 patients with LN enrolled in IRB-approved protocols at the NIDDK between 1976 and 1999. The specimens were divided in two groups based on histological chronicity index (CI). CI ≥ 4 were categorized as having high degree of chronicity of chronic kidney injury. 18 kidneys from 8 patients including high CI (n=9) and low CI (n=9) were used for miR profiling by Affymetrix microRNA microarrays.
2012-12-01 | E-GEOD-42648 | biostudies-arrayexpress
Project description:These data show that the genes that distinguish myofibroblasts from fibroblasts are myriad, and that some genes not traditionally associated with myofibroblast differentiation may serve as novel therapeutic targets for fibrosing disorders. Gene expression levels were assessed from total RNA on the Affymetrix U219 microarray. Here, we use transforming growth factor-β1 (TGF-β1) and prostaglandin E2 (PGE2), which has recently been shown to reverse myofibroblast differentiation, to investigate the transcriptomic changes that occur during TGF-β1-induced differentiation and PGE2-induced de-differentiation of myofibroblasts.
2015-06-30 | E-GEOD-63659 | biostudies-arrayexpress
Project description:Background: Differentiation of fibroblasts into myofibroblasts is necessary for wound healing, but excessive myofibroblast presence and persistence can result in scarring. Treatment for scarring is limited largely due to a lack of comprehensive understanding of how fibroblasts and myofibroblasts differ at the transcript level. The purpose of the study was to comprehensively characterize transcriptional profiles of injured fibroblasts relative to normal fibroblasts, utilizing fibroblasts from the vocal fold as a model for other areas of the body. Results: we identified differentially expressed genes between groups of normal fibroblasts, scarred fibroblasts, and fibroblasts treated with transforming growth factor-beta 1 (TGF-β1), which represented an induced-scar phenotype. Principal component analysis revealed clustering of normal fibroblasts separate from the clustering of fibroblasts treated with TGF-β1; scarred fibroblasts were more similar to normal fibroblasts than fibroblasts treated with TGF-β1. Enrichment analyses revealed pathways related to cell signaling, receptor-ligand activity, and regulation of cell functions in scarred fibroblasts, pathways related to cell adhesion in normal fibroblasts, and pathways related to ECM binding in fibroblasts treated with TGF-β1. Although transcriptomic profiles between scarred fibroblasts and fibroblasts treated with TGF-β1 were relatively dissimilar, the most highly co-expressed genes were enriched in pathways related to actin cytoskeleton binding. Conclusions: Transcriptomics of normal fibroblasts differ from myofibroblasts, including from those retrieved from scar and those treated with TGF-β1. Despite large differences in transcriptomics between tVFF and sVFF, tVFF serve as a useful in vitro model of myofibroblasts and highlight key similarities to myofibroblasts extracted from scar pathology, as well as expected differences related to normal fibroblasts from healthy VF.
2025-03-25 | GSE278852 | GEO
Project description:Background: Increased Galectin 3-binding protein (Lgals3bp) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor-β1 (TGF-β1) in the emergence of these diseases, the present study tested the hypothesis that Lgals3bp regulates the TGF-β1 signaling pathway. Methods: The expression levels of Lgals3bp and TGF-β1 were analyzed in patients with non-alcoholic steatohepatitis (NASH) and HCC. Multiple omics techniques, such as RNA-sequencing, transposase-accessible chromatin-sequencing assay, and liquid chromatography-tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the Lgals3bp-TGF-β1 axis. Moreover, the effects of altered TGF-β1 signaling in chronic inflammatory conditions were investigated in conditional Lgals3bp-knockin and Lgals3bp-knockout mice. Results: In patients with NASH and HCC, the levels of Lgals3bp and TGF-β1 exhibited positive correlations. Stimulation of Lgals3bp by the inflammatory cytokine interferon α in HCC cells or ectopic overexpression of Lgals3bp in hepatocytes promoted the expression levels of TGFB1. Aggravated fibrosis was observed in the livers of hepatocyte-specific Lgals3bp knock-in mice, with increased TGF-β1 levels. Lgals3bp directly bound to and assembled integrin αV, an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin cytoskeleton. The released TGF-β1 activated JunB transcription factor, which in turn promoted the TGF-β1 positive feedback loop. Lgals3bp deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced fibrosis. Finally, Lgals3bp depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β1. Conclusion: Lgals3bp plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway, making it a promising therapeutic target in TGF-β1-related diseases.
2024-07-06 | GSE271354 | GEO
Project description:Background: Increased Galectin 3-binding protein (Lgals3bp) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor-β1 (TGF-β1) in the emergence of these diseases, the present study tested the hypothesis that Lgals3bp regulates the TGF-β1 signaling pathway. Methods: The expression levels of Lgals3bp and TGF-β1 were analyzed in patients with non-alcoholic steatohepatitis (NASH) and HCC. Multiple omics techniques, such as RNA-sequencing, transposase-accessible chromatin-sequencing assay, and liquid chromatography-tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the Lgals3bp-TGF-β1 axis. Moreover, the effects of altered TGF-β1 signaling in chronic inflammatory conditions were investigated in conditional Lgals3bp-knockin and Lgals3bp-knockout mice. Results: In patients with NASH and HCC, the levels of Lgals3bp and TGF-β1 exhibited positive correlations. Stimulation of Lgals3bp by the inflammatory cytokine interferon α in HCC cells or ectopic overexpression of Lgals3bp in hepatocytes promoted the expression levels of TGFB1. Aggravated fibrosis was observed in the livers of hepatocyte-specific Lgals3bp knock-in mice, with increased TGF-β1 levels. Lgals3bp directly bound to and assembled integrin αV, an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin cytoskeleton. The released TGF-β1 activated JunB transcription factor, which in turn promoted the TGF-β1 positive feedback loop. Lgals3bp deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced fibrosis. Finally, Lgals3bp depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β1. Conclusion: Lgals3bp plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway, making it a promising therapeutic target in TGF-β1-related diseases.
2024-07-06 | GSE271352 | GEO