Tissue Transcriptome Driven Identification of Epidermal Growth Factor as a Chronic Kidney Disease Biomarker
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE69438 | GEO | 2015/12/14
SECONDARY ACCESSION(S): PRJNA285492
REPOSITORIES: GEO
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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
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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.
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