Tissue Transcriptome Driven Identification of Epidermal Growth Factor as a Chronic Kidney Disease Biomarker
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE69438 | GEO | 2015/12/14
SECONDARY ACCESSION(S): PRJNA285492
REPOSITORIES: GEO
Similar Datasets
Project description:We identified EGF as the top candidates predicting kidney function through an intrarenal transcriptome-driven approach, and demonstrated it is an independent risk predictor of CKD progression and can significantly improve prediction of renal outcome by established clinical parameters in diverse populations with CKD from a wide spectrum of causes and stages Chronic Kidney Disease, Lupus nephritis, Focal and Segmental Glomerulosclerosis, Nephropathies, Membranous Glomerulonephritis. This dataset is part of the TransQST collection.
2015-12-14 | E-GEOD-69438 | biostudies-arrayexpress
Project description:In this study, we further verified the role of LIF by looking at gene expressions in morula stage embryos through DNA microarray. Our results showed that LIF knockdown affected 373 gene expressions, and after LIF supplementation we found that the epidermal growth factor (EGF) is most affected by LIF expression. In order to observe the correlation between LIF and EGF, the LIF knockdown embryos were supplemented with various growth factors including LIF, EGF, GM-CSF, TGF, and IGF II. Only LIF and EGF caused the rate of blastocyst development to recover from 52% of control significantly to 83% and 93%, respectively, and all of the parameters, such as the diameter of blastocysts, the numbers of blastomeres, and cells in ICM and TE, to mostly be restored. Moreover, EGF knockdown also impaired blastocyst development which was reversed by LIF or EGF supplementation. These data suggest that the two growth factors EGF and LIF can be compensatory to each other during early embryonic development, and one of them is necessary for sustaining the normal development of preimplantation embryos.
2015-09-01 | GSE71736 | GEO
Project description:MicroRNAs (miRNAs) are small regulatory RNA molecules that modulate the activity of specific mRNA targets and play important roles in a wide range of physiologic and pathologic processes. We hypothesized that miRNAs might be involved in the progression of CKD. In our previous studies we found chronic renal damages developed progressively in rats with 5/6 nephrectomy. L-mimosine(L-Mim) intervention from wk 5 to wk 12 improved renal function and resulted in additional accumulation of HIF-1 M-NM-1 and -2 M-NM-1 at wk 12. In the current study we found miR-29c was up-regulated in the L-Mim treated group compared with the control using Agilent miRNA microarrays. Of the microRNAs and proteins that exhibited reciprocal changes in expression following the L-Mim treatment, miR-29c and tropomyosin 1M-NM-1 (TPM1), which is involved in stress fiber function, met the sequence criteria for microRNA-target interaction, were later confirmed by 3'-untranslated region reporter analysis. TGFM-NM-21 treatment (3 ng/ml, 24 hours) decreased miR-29c expression and up-regulated protein expression of TPM1 in human renal epithelial cells. Overexpression of miR-29c significantly attenuated TGF-M-NM-21 induced increase in TPM1 in vitro. Moreover, intrarenal expression of miR-29c was decreased in IgAN patients with moderate to severe tubulointerstital fibrosis (TIF), compared with IgAN patients without TIF, and intrarenal protein expression of TMP1 was significantly increased in IgAN patients with TIF. The results suggest that intrarenal expression of miR-29c was down-regulated while its predicted target, TPM1 was up-regulated in the progression of CKD. Short term stabilizing of HIF up-regulates miR-29c and attenuates CKD in the remnant kidney model. Four weeks after 5/6 nephrectomy, rats were treated with intraperitoneal injections of vehicle or L-mimosine (L-Mim, Calbiochem), a prolyl 4-hydroxylase inhibitor (PHD), at a dosage of 50 mg/kg every other day. At the end of wk 12 after 5/6 nephrectomy, all rats (n=4, for each group) were sacrificed and blood samples were collected via cardiac puncture. Renal tissue were harvested, one piece of which was fixed in neutral formalin and then embedded in paraffin. The remaining kidney tissue was dissected in ice-cold PBS to, remove medulla, and then snap-frozen in liquid nitrogen before transferring to storage at -80M-BM-0C until further analysis.
2013-01-08 | E-GEOD-28471 | biostudies-arrayexpress
Project description:In this study, we further verified the role of LIF by looking at gene expressions in morula stage embryos through DNA microarray. Our results showed that LIF knockdown affected 373 gene expressions, and after LIF supplementation we found that the epidermal growth factor (EGF) is most affected by LIF expression. In order to observe the correlation between LIF and EGF, the LIF knockdown embryos were supplemented with various growth factors including LIF, EGF, GM-CSF, TGF, and IGF II. Only LIF and EGF caused the rate of blastocyst development to recover from 52% of control significantly to 83% and 93%, respectively, and all of the parameters, such as the diameter of blastocysts, the numbers of blastomeres, and cells in ICM and TE, to mostly be restored. Moreover, EGF knockdown also impaired blastocyst development which was reversed by LIF or EGF supplementation. These data suggest that the two growth factors EGF and LIF can be compensatory to each other during early embryonic development, and one of them is necessary for sustaining the normal development of preimplantation embryos. Two-condition experiment, mouse embryos vs. LIF-deficiency mouse embryos at morula stage
2015-09-01 | E-GEOD-71736 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small regulatory RNA molecules that modulate the activity of specific mRNA targets and play important roles in a wide range of physiologic and pathologic processes. We hypothesized that miRNAs might be involved in the progression of CKD. In our previous studies we found chronic renal damages developed progressively in rats with 5/6 nephrectomy. L-mimosine(L-Mim) intervention from wk 5 to wk 12 improved renal function and resulted in additional accumulation of HIF-1 α and -2 α at wk 12. In the current study we found miR-29c was up-regulated in the L-Mim treated group compared with the control using Agilent miRNA microarrays. Of the microRNAs and proteins that exhibited reciprocal changes in expression following the L-Mim treatment, miR-29c and tropomyosin 1α (TPM1), which is involved in stress fiber function, met the sequence criteria for microRNA-target interaction, were later confirmed by 3'-untranslated region reporter analysis. TGFβ1 treatment (3 ng/ml, 24 hours) decreased miR-29c expression and up-regulated protein expression of TPM1 in human renal epithelial cells. Overexpression of miR-29c significantly attenuated TGF-β1 induced increase in TPM1 in vitro. Moreover, intrarenal expression of miR-29c was decreased in IgAN patients with moderate to severe tubulointerstital fibrosis (TIF), compared with IgAN patients without TIF, and intrarenal protein expression of TMP1 was significantly increased in IgAN patients with TIF. The results suggest that intrarenal expression of miR-29c was down-regulated while its predicted target, TPM1 was up-regulated in the progression of CKD. Short term stabilizing of HIF up-regulates miR-29c and attenuates CKD in the remnant kidney model.
2013-01-08 | GSE28471 | GEO
Project description:Each year in the United States, more than 530,000 babies are born prior to full 37 weeks of gestation. One of the major problems associated with prematurity is the development of a condition known as necrotizing enterocolitis (NEC). In 50% of infants with NEC a large amount of damaged and dead intestine must be surgically removed, often resulting in death or lifelong health problems. A growing body of experimental and clinical evidence supports a conclusion that deficient quantities of epidermal growth factor (EGF) leads to the development of NEC. The EGF peptide appears to be fundamental for normal intestinal development and repair. Soy-milk containing engineered EGF may be a suitable therapy if given to premature infants to prevent NEC. Human mature EGF is 6 kDa protein with three intramolecular disulfide bonds. To produce EGF a synthetic codon-optimized gene was transferred to soybean by biolistic transformation. The resulting transgenic lines were regenerated into somatic embryos that were screened by PCR and the production of EGF assayed by ELISA. Crude extracts of somatic embryos producing EGF were assessed for bioactivity by induction of phosphorylation of the EGF receptor in HeLa cells that showed soy-produced EGF exhibited the same activity as authentic EGF. T0 transgenic EGF seeds have showed positive ELISA for EGF demonstrating the feasibility to produce a therapeutic soy-milk to mitigate the development of NEC by premature infants. The next stage of this project will test the efficacy of Soy/EGF in an animal model for short bowel syndrome.
2016-06-22 | PXD003326 | Pride
Project description:Objective: A subset of Crohns disease (CD) patients experiences long-term remission after infliximab withdrawal. Biomarkers are needed to identify those patients.Design: New biomarkers of relapse were searched in the baseline serum of CD patients stopping infliximab when they were under combined therapy (antimetabolite and infliximab) and stable clinical remission (STORI cohort, n=102). From shotgun proteomics experiment (discovery step), biomarker candidates were identified and further targeted by selected reaction monitoring (verification step). The dataset was stratified to search for markers of short- (<6 months) or long-term relapse (>6 months). The risk of relapse and the predicting capacity associated with biomarker candidates were evaluated using univariate Cox model and log-rank statistic, respectively. To test their complementary predicting capacity, biomarker candidates were systematically combined in pairs. Results: Distinct biomarker candidates were associated with the risk (hazard ratio: HR) of short- (15 proteins, 2.9<HR<16.1, p<0.05) and long-term (17 proteins, 2<HR<4.4, p<0.05) relapse, they reflect different pathophysiological processes. In stratified and non-stratified datasets, novel marker combinations exhibited a high predicting capacity as shown by their higher Z-scores (FDR<0.001) than CRP and faecal calprotectin (current references in predicting relapse). Conclusion: We identified for the first time circulating biomarker candidates associated with the risk of long-term relapse in CD patients stopping infliximab. We also highlight a sequence of pathophysiological processes leading to relapse, this could help to better understand the disease progression. Our findings may pave the way for a better non-invasive evaluation of the risk of relapse when contemplating anti-TNFα withdrawal in CD patients.
2020-10-19 | PXD019008 | Pride
Project description: Not available
| S-EPMC4861144 | biostudies-literature
Project description:Hematopoietic aging is associated with decreased hematopoietic stem cell (HSC) self-renewal capacity and increased risk for myelodysplasia and leukemia. Deficient DNA repair contributes to the decline in HSC self-renewal capacity during aging and it remains unclear whether extrinsic signals can rejuvenate aged HSCs. Here, we demonstrate that augmentation of non-homologous end-joining (NHEJ) DNA repair in aged HSCs via treatment with epidermal growth factor (EGF) rejuvenates HSC function. Seven day culture of BM CD34-ckit+sca-1+lin- (34-KSL) HSCs from aged C57BL/6 mice with EGF suppressed myeloid skewing and increased production of multipotent CFU-granulocyte, erythroid, monocyte and megakaryocyte (CFU-GEMM) colonies. Aged, EGF-treated HSCs displayed increased donor multilineage engraftment in primary competitively transplanted mice and in secondary mice compared to mice transplanted with aged, control HSCs. Donor cell engraftment within the bone marrow (BM) KSL and SLAM+KSL HSC population was > 2-fold increased in mice transplanted with aged, EGF-treated HSCs. Systemic administration of EGF to aged mice for 6 weeks also increased long term – HSC self-renewal capacity as measured by increased donor bone marrow (BM) competitive repopulation in primary and secondary transplanted mice. Conversely, deletion of EGFR in Scl/Tal1+ hematopoietic cells was associated with increased myeloid skewing and depletion of LT-HSCs in middle aged mice. Mechanistically, EGF treatment decreased DNA damage in aged HSCs through activation of DNA PK-cs, Artemis and NHEJ repair. Inhibition of DNA PK-cs blocked EGF-mediated restoration of multipotent differentiation and suppression of myeloid skewing in aged HSCs, suggesting that the restoration of hematopoietic potential in aged HSCs is dependent on EGF-mediated activation of DNA PK-cs. EGF treatment also converted the transcriptome of aged HSCs from enrichment for genes involved in cell death and survival to genes involved in HSC generation and identity. These data suggest that extrinsic activation of EGFR signaling can restore key functional capacities in aged HSCs.
2024-04-01 | GSE252293 | GEO
Project description:Primary cultures of astrocytes from rat optic nerve heads were treated with EGFR ligand, EGF. Two cell lines from two different rat donors were used. The sister cell cultures were set as control and EGF treated groups. Experiment Overall Design: experiment #1: compared control astrocyte cultures to sister cultures treated with EGF for 4 hours. Experiment Overall Design: experiment #2: compared control astrocyte cultures to sister cultures treated with EGF for 12 hours
2007-11-29 | E-GEOD-5282 | biostudies-arrayexpress