Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA318503 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Progressive loss of tissue homeostasis hallmarks numerous age-related pathologies. By using parabiosic approaches in animal models, recent evidences demonstrate that age-regulated geronic factors such as GDF11 or CCL11 could widely control positively or negatively tissue homeostasis. Here we evaluated the impact of the first identified anti-geronic hormone a-Klotho on tissue homeostasis taken articular cartilage and osteoarthritis (OA) as studying models. We show that a-Klotho is secreted during an in vitro induced chondrogenesis of osteo-chondral stem cells. Expression of a-Klotho is reduced in both cartilage of OA patients compared to healthy donors and in cartilage of OA murine models. Gain and loss of function experiments followed by a genome-wide gene array analysis identified Nos2-Zip8-MMP13 catabolic axis as repressed in OA chondrocytes upon a-Klotho treatment. Accordingly, intra-articular delivery of secreted a-klotho delays cartilage loss of functions in experimental OA mouse models thus revealing a novel chondroprotective function for this anti-geronic hormone.
2018-01-21 | GSE80285 | GEO
Project description:α-Klotho has emerged as a powerful regulator of the ageing process. To-date, the expression profile of α-Klotho in human tissues is unknown and its existence in some human tissue types is subject to much controversy. Objective: This is the first study to characterize system-wide tissue expression of transmembrane α-Klotho in humans. We have employed next generation targeted proteomic analysis using Parallel Reaction Monitoring (PRM) in parallel with conventional antibody-based methods to determine the expression and spatial distribution of human α-Klotho expression in health. Results: The distribution of α-Klotho in human tissues from various organ systems, including arterial, epithelial, endocrine, reproductive and neuronal tissues was first identified by immunohistochemistry. Kidney tissues showed strong α-Klotho expression, while liver did not reveal a detectable signal. These results were next confirmed by western blotting of both whole tissues and primary cells. To validate our antibody-based results, α-Klotho expressing tissues were subjected to PRM mass spectrometry identifying peptides specific for the full length, transmembrane α-Klotho isoform. Conclusions: The data presented confirms α-Klotho expression in the kidney tubule and in artery, and provides evidence of α-Klotho expression across organ systems and cell-types that have not previously been described in humans.
2015-10-13 | PXD002775 | Pride
Project description:Long non-coding RNA (lncRNA) play an important role in several biological processes including some renal diseases. Nevertheless, little is known on lncRNAs that are expressed in healthy kidney and involved in renal cell homeostasis and development and even less is known about lncRNA involved in the maintenance of human adult renal stem/progenitor cells (ARPCs). ARPCs have been shown to be very important for renal homeostasis and repair processes thanks to their self-renewal and differentiative ability as well as their capacity to secrete different reparative factors depending on the type of damage. Through a whole genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved cell cycle and senescence biological processes. We then generated HOTAIR knock-out ARPC lines by CRISPR/Cas9 genome editing and showed that this lncRNA limits the apoptotic process of ARPCs and sustains their proliferative capacity, thus resulting responsible of their self-renewal properties. In addition, we found that the knockout of HOTAIR led to the ARPC senescence and to a significant decrease of the CD133 stem cell marker expression that is an inverse marker of ARPC senescence and can regulate renal tubular repair after the damage. Moreover, we found that ARPCs expressed high levels of the α-Klotho anti-aging protein and especially 2.6 fold higher levels compared to that secreted by RPTECs. The HOTAIR knockout in ARPCs leads to lower α-Klotho levels, comparable to that of RPTECs. Finnally we showed that HOTAIR induces epigenetic silencing of the cell cycle inhibitor p15 through the trimethylation of the histone H3K27. Altogether, these results shed new light on these important renal cells and may support the future development of precision therapies for kidney diseases.
2023-01-06 | E-MTAB-11451 | biostudies-arrayexpress
Project description:Klotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here we examined the effects of Klotho on MO3.13, a human oligodendroglioma cell line in order to determine the potential role of Klotho as a tumor suppressor. We show that exogenous Klotho affects the ERK and Akt signaling pathways and decreases the proliferative abilities of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80% of the differentially expressed genes being downregulated. Using gene set enrichment analysis we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain malignancies. 6 Samples
2014-06-09 | E-GEOD-51536 | biostudies-arrayexpress
Project description:Notch signaling modulates skeletal formation and osteoarthritis (OA) development through induction of catabolic factors. Here we examined functional roles of Hes1, the representative downstream transcription factor of Notch signaling, during these processes. Chromatin immunoprecipitation-sequencing (ChIP-seq) identified resposive elements of Hes1 around gene loci of Mmp13 and Adamts5, which were catabolic enzymes of cartilage matrix. Examination of HES1 binding site in human chondrogenic SW1353 cells.
2014-08-02 | E-GEOD-60006 | biostudies-arrayexpress
Project description:Notch signaling modulates skeletal formation and osteoarthritis (OA) development through induction of catabolic factors. Here we examined functional roles of Hes1, the representative downstream transcription factor of Notch signaling, during these processes. Chromatin immunoprecipitation-sequencing (ChIP-seq) identified resposive elements of Hes1 around gene loci of Mmp13 and Adamts5, which were catabolic enzymes of cartilage matrix.
2014-08-02 | GSE60006 | GEO
Project description:Klotho functions as an aging suppressor, which, in mice, extends lifespan when overexpressed and accelerates development of aging-like phenotypes when disrupted. Klotho is mainly expressed in brain and kidney and is secreted into the serum and CSF. We have previously shown that Klotho is reduced in brains of old monkeys, rats and mice. We further reported the ability of Klotho to enhance oligodendrocyte differentiation and myelination. Here we examined the effects of Klotho on MO3.13, a human oligodendroglioma cell line in order to determine the potential role of Klotho as a tumor suppressor. We show that exogenous Klotho affects the ERK and Akt signaling pathways and decreases the proliferative abilities of MO3.13 cells. Furthermore, microarray analysis of Klotho-treated MO3.13 cells reveals a massive change in gene expression with 80% of the differentially expressed genes being downregulated. Using gene set enrichment analysis we predicted potential transcription factors involved in regulating Klotho-treated MO3.13 cells and found that these cells are highly enriched in the gene sets, that are similarly observed in cancer, cardiovascular disease, stress, aging and hormone-related chemical and genetic perturbations. Since Klotho is downregulated in all brain tumors tested to date, enhancing Klotho has therapeutic potential for treating brain malignancies.
2014-06-09 | GSE51536 | GEO
Project description:Mutations of the β-glucuronidase protein α-Klotho have been associated with premature aging, and altered cognitive function. Although highly expressed in specific areas of the brain, Klotho functions in the central nervous system remain unknow. Here, we show that cultured hippocampal neurons respond to insulin and glutamate stimulation by elevating Klotho protein levels. Conversely, AMPA and NMDA antagonism suppress neuronal Klotho expression. We also provide evidence that soluble Klotho enhances astrocytic aerobic glycolysis by hindering pyruvate metabolism through the mitochondria, and stimulating its processing by lactate dehydrogenase. Pharmacological inhibition of FGFR1, Erk phosphorylation, and monocarboxylic acid transporters prevents Klotho-induced lactate release from astrocytes. Taken together these data suggest Klotho is a potential new player in the metabolic coupling between neurons and astrocytes. Neuronal glutamatergic activity and insulin modulation elicit Klotho release, which in turn stimulates astrocytic lactate formation and release. Lactate can then be used by neurons as a metabolic substrate contributing to fulfill their elevated energy requirements.
2018-03-08 | GSE100046 | GEO
Project description:Pdx1 maintains β-cell identity and function by repressing an α-cell program
| PRJNA227298 | ENA
Project description:In the tumor microenvironment, Cancer Associated Fibroblasts (CAFs) become activated by cancer cells and increase their secretory activity to produce soluble factors that contribute to tumor cells proliferation, invasion and dissemination to distant organs. The pro-tumorigenic transcription factor STAT3 and its canonical inducer, the pro-inflammatory cytokine IL-6 act conjunctly in a positive feedback loop that maintains high levels of IL-6 secretion and STAT3 activation in both tumor and stromal cells. Here, we demonstrate that STAT3 is essential for the pro-tumorigenic functions of murine breast cancer CAFs both in vitro and in vivo, and identify a STAT3 signature significantly enriched for genes encoding for secreted proteins. Among those, IL-6, ANGPTL4, STC-1 and MMP13 were validated as STAT3-dependent mediators of CAF pro-tumorigenic functions by different approaches. CAFs activities were moreover impaired by IL-6 Receptor blocking antibodies and by MMP13 inhibition, supporting the feasibility of a therapeutic approach based on inhibiting STAT3-induced CAF-secreted proteins. The usefulness of such an approach is supported by the observation that an equivalent CAF-STAT3 signature in humans is expressed at high levels in breast cancer stromal cells and characterizes patients with a shorter disease specific survival, including those with basal-like disease.
2021-12-31 | GSE178081 | GEO