Early adipogenesis is regulated through the newly identified FHL2-NFAT5 signaling complex
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ABSTRACT:
PROVIDER: PRJNA827188 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18774385_1.fastq.gz | Fastqsanger.gz | |||
| SRR18774385_2.fastq.gz | Fastqsanger.gz | |||
| SRR18774386_1.fastq.gz | Fastqsanger.gz | |||
| SRR18774386_2.fastq.gz | Fastqsanger.gz | |||
| SRR18774387_1.fastq.gz | Fastqsanger.gz |
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Project description:The LIM-domain-only protein FHL2 is a modulator of signal transduction and has been shown to direct the differentiation of mesenchymal stem cells toward osteoblasts and myocytes phenotypes. We hypothesized that FHL2 may simultaneously interfere with the induction of the adipocyte lineage. Therefore, we investigated the role of FHL2 in adipocyte differentiation using pre-adipocytes isolated from mouse adipose tissue and the 3T3-L1 (pre)adipocyte cell line. Here we report that FHL2 is expressed in pre-adipocytes and for accurate adipocyte differentiation, this protein needs to be downregulated during the early stages of adipogenesis. More specifically, constitutive overexpression of FHL2 drastically inhibits adipocyte differentiation in 3T3-L1 cells, which was demonstrated by suppressed activation of the adipogenic gene expression program as shown by extensive RNAseq analyses, and diminished lipid accumulation. To identify the protein-protein interactions mediating this repressive activity of FHL2 on adipogenesis, we performed affinity-purification mass spectrometry (AP-MS). This analysis revealed the interaction of FHL2 with the Nuclear factor of activated T-cells 5 (NFAT5), an established inhibitor of adipocyte differentiation. NFAT5 knockdown rescued the inhibitory effect of FHL2 overexpression on 3T3-L1 differentiation, indicating that these proteins act cooperatively. In conclusion, we present a new regulatory function of FHL2 in early adipocyte differentiation and revealed that FHL2-mediated inhibition of pre-adipocyte differentiation is dependent on its interaction with NFAT5.
2023-11-13 | PXD033974 | Pride
Project description:To investigate the effect of FHL2 overexpression in the regulation of adipogenic differentiation, we established a stable cell line overexpressing FHL2-GFP and CTRL-GFP by lentiviral transduction.
2023-02-24 | GSE200920 | GEO
Project description:Characteristics of differentiated newly identified adipose precursor cells
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Project description:The LIM-only protein FHL2 acts as a transcriptional modulator that positively or negatively regulates multiple signaling pathways. We recently reported that FHL2 cooperates with CBP/p300 in the activation of ß-catenin/TCF target gene cyclin D1. In this paper, we demonstrate that FHL2 is associated with the cyclin D1 promoter at the TCF/CRE site, providing evidence that cyclin D1 is a direct target of FHL2. We show that deficiency of FHL2 greatly reduces the proliferative capacity of spontaneously immortalized mouse fibroblasts which is associated with decreased expression of cyclin D1 and p16INK4a, and hypophosphorylation of Rb. Reexpression of FHL2 in FHL2-null fibroblasts efficiently restores cyclin D1 levels and cell proliferative capacity, indicating that FHL2 is critical for cyclin D1 activation and cell growth. Moreover, ectopic cyclin D1 expression is sufficient to override growth inhibition of immortalized FHL2-null fibroblasts. Gene expression profiling revealed that FHL2 deficiency triggers a broad change of the cell cycle program that is associated with downregulation of several G1/S and G2/M cyclins, E2F transcription factors and DNA replication machinery, thus correlating with reduced cell proliferation. This change also involves downregulation of the negative cell cycle regulators, particularly INK4 inhibitors, which could counteract the decreased expression of cyclins, allowing cells to grow. Our study illustrates that FHL2 can act on different aspects of the cell cycle program to finely regulate cell proliferation. Keywords: mouse embryonic fibroblasts derived from FHL2-/- and WT mouse embryos (14.5 days)
2008-06-06 | GSE10902 | GEO
Project description:Four-and-a-Half-LIM-domain-protein 2 (FHL2) modulates multiple signal transduction pathways but has not been implicated in obesity or energy metabolism. In man, FHL2 expression increases with age and high FHL2 expression is associated with increased body weight in human and mice, leading us to hypothesize that FHL2 is a determinant of diet-induced obesity. Accordingly, loss of FHL2 protects mice from high-fat diet-induced weight gain. This is associated with enhanced energy expenditure in FHL2-/- mice. In an attempt to discover the origin of the increased energy expenditure in FHL2-/- mice, we performed transcriptome analysis (RNA-seq) on the heart, since FHL2 is highly expressed in this organ and gonadal white adipose tissue in WT and FHL2-/- mice.
2021-06-14 | GSE156027 | GEO
Project description:FHL2 is known to be deregulated in liver cancer. In the present study, microarray gene expression profiling was performed to identify the genes regulated downstream of FHL2 In this dataset, we compared the RNA samples from livers of FHL2 knockout mice and those of wild-type (WT) mice.
2012-01-01 | GSE26904 | GEO
Project description:NFAT5 is an osmoprotective transcription factor whose DNA binding domain shares structural homology with NFkappaB and other member of NFAT family, but its role in chronic inflammatory diseases remains unclear. The mRNA profiling of synoviocytes and endothelial cells transfected with NFAT5-targeted siRNA reveals three major changes in cellular processes associated with the pathogenesis of rheumatoid arthritis: cell cycle and survival, angiogenesis, and cell migration. The cells were transfected with NFAT5-targeted siRNA or non-specific scrambled (control) siRNA.
2010-12-31 | E-GEOD-22956 | biostudies-arrayexpress
Project description:The LIM-only protein FHL2 is expressed in SMCs and inhibits SMC-rich lesion formation. However, the underlying mechanism behind FHL2's action in SMCs has been only partially resolved. To further elucidate the role of FHL2 in SMCs we compared the transcriptome of cultured SMCs derived from wild-type (WT) and FHL2-knockout (KO) mice.
2014-10-07 | GSE56860 | GEO
Project description:FHL2 is known to be deregulated in liver cancer. In the present study, microarray gene expression profiling was performed to identify the genes regulated downstream of FHL2 In this dataset, we compared the RNA samples from livers of FHL2 knockout mice and those of wild-type (WT) mice. FHL2 knockout mice was initially generated by Chu et al. 2000. RNA from three mice per group (male, age: 10-11 weeks) were pooled and the two groups were subjected to analysis .
2012-01-01 | E-GEOD-26904 | biostudies-arrayexpress
Project description:Homeostatic control of intracellular ionic strength is essential for protein, organelle and genome function, yet mechanisms that sense and enable adaptation to ionic stress remain poorly understood in animals. We find that the transcription factor NFAT5 directly senses solution ionic strength using a C-terminal intrinsically disordered region. Both in intact cells and in a purified system, NFAT5 forms dynamic, reversible biomolecular condensates in response to increasing ionic strength. This self-associative property, conserved from insects to mammals, allows NFAT5 to accumulate in the nucleus and activate genes that restore cellular ion content. Mutations that reduce condensation or those that promote aggregation both reduce NFAT5 activity, highlighting the importance of optimally tuned associative interactions. To investigate the composition of NFAT5 condensates in response to hypertonic stress, proteins in close proximity of NFAT5 were identified using a variant of NFAT5 fused to TurboID as bait. Hypertonic stress increases NFAT5 proximity to protein complexes belonging to the GO gene sets of “transcription coactivator activity” and “positive regulation of DNA templated transcription initiation.” Closer inspection revealed that the association between NFAT5 and two transcriptional co-activators (the mediator complex and BRD4) and RNAPII itself increased in response to hypertonic stress.
2025-04-17 | PXD052591 | Pride