Plasma-specific microRNA responses in rats treated with acute toxicity doses of aristolochic acid I
ABSTRACT: In the present study, goal was to scan the potential biomarker for acute kidney injury induced by aristolochic acid I (AAI).We utilized the microarry analysis to investigate the microRNA (miRNA) expression profile in kidneys from rat treated by 40mg/kg AA I for 2-6 days. miRNAs with significantly different expression of global miRNA expression profile were validated by qRT-PCR. For miRNAs still significantly disregulation, we further examined the expression in plasma of rats treated with AAI dosed at 10, 20 and 40mg/kg AAI for 2-6 days by qRT-PCR. miRNAs with significantly dysregulation in plasma, their expression in brain, liver and heart was examined for kicking out the non-specific disregulation in AAI induced acute kidney injury, so that the significant dysregulation miRNAs with specificity in kidney and plasma was found as potential biomarkers for AAI induced acute kidney injury. Five control and 15 kidneys treated with 40mg/kg AAI on day 2, 4 and 6 was examined by microarray.
Project description:MicroRNAs (miRNAs) expression profiles are widely investigated in the major cancers, but their specific roles and functions in cancers have not yet to be fully elucidated. We investigated expression profiles of miRNAs in clear cell renal cell carcinomas (ccRCCs) and in matched normal kidney tissues (NCTs) by using a miRNAs microarray platform which covers a total of 851 human miRNAs. Tumor tissue samples were immediately snap-frozen in liquid nitrogen after surgery, and then stored in a deep freezer at -80°C. Total RNA was extracted from 5 ccRCC tissues and paired NCTs and expression profiles of miRNAs were screened by using a miRNA microarray platform.
Project description:Contrast-induced acute kidney injury (CI-AKI) is typically defined by an increase in serum creatinine (SCr) after intravascular administration of contrast medium. Since creatinine is an unreliable indicator for acute changes in kidney function, an early biomarkers for CI-AKI diagnosis is important for initiating therapy.We assessed the hypothesis that circulating microRNAs (miRNAs) could be served as potential biomarkers to early detect CI-AKI.The rat model of acute kidney injury was developed as we previously described. We first detect miRNA profile of plasma and kidney tissue using Agilent microarray platform. 3 miRNA species with > 1.5-fold increase in plasma samples of CI-AKI rats, including miRNA-30a, miRNA-30e and miRNA-188, were selected as candidate miRNAs of potential biomarkers. 24 rats were randomly divided into 2 groups (CI-AKI group and control group), each with 4 subgroups (n=3). Peripheral blood and kidney samples were harvest at 8h after contrast medium/normal saline administration. Total RNA sample from each rat in the same subgroup was combined together as pooled sample for further test. The Agilent microarray platform was adapted to profile the miRNA spectra.
Project description:Drug resistance, caused by complex and redundant mechanisms, is a major obstacle in cancer treatment, especially in liver and kidney cancers. Combinational therapy of miRNAs, which concurrently target multiple pathways, with anticancer drugs represent a new strategy to improve the drug response. By a systems approach, we identified that miR-27b, a miRNA deleted in liver and kidney cancers, sensitizes cancer cells to a broad spectrum of anticancer drugs in vitro and in vivo. Two samples transfected with nontarget miRNA control or miR-27b mimics followed by 48 hours doxorubicin treatment
Project description:MicroRNAs (miRNAs) are a class of small non-coding single-stranded RNAs whose dysregulation of expression plays an important role in cancer development. Circulating miRNAs are novel biomarkers in several cancers. Thus, we explored whether the miRNAs in plasma could be useful clinical biomarkers for multiple myeloma (MM) patients. The expression levels of four miRNAs in plasma were upregulated while eight miRNAs were downregulated in MM patients compared with healthy controls according to microarray. MiRNA microarray was conducted to determine deregulated miRNAs in plasma of 9 MM patients and 7 healthy controls.
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. 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 -80°C until further analysis.
Project description:Gadd45a can enhance somatic cell reprogramming significantly. To explore the roles of Gadd45a playing in reprogramming, we performed miRNA microarray to identify miRNAs and signals pathways that regulated by Gadd45a. miRNAs expression of MEFs was measured at day8 in reprogramming. Four samples were set: MEFs infected with SKO plus Flag, MEFs infected with SKO plus Gadd45a, MEFs infected with SKOM plus Flag and MEFs infected with SKOM+Ga.
Project description:To identify miRNAs differentially expressed in cholangiocarcinoma,3 human cholangiocarcinoma and their corresponding normal bile duct tissues were obtained from 3 patients after operation with postoperative pathological diagnosed perihilar or distal biliary cholangiocarcinoma miRNAs expression in human cholangiocarcinoma/normal bile duct samples was measured after operation.Three independent experiments were performed using different patients for each experiment.
Project description:To further explain pathology of mTORC1 -stimulated osteoarthritis, we have employed whole genome microarray expression profiling as a discovery platform to identify miRNAs which involved in development of mTORC1-stimulated osteoarthritis We generated Col2a1-specific deletion of Tsc1 mice. mTORC1 induced miRNAs expression in development of osteoarthritis was measured at eight weeks after birth. Independent experiments were performed using knee joint cartilage from Col2a1Tsc1KO and control mice.
Project description:To investigate the gene expression profile of genamycin induced nephrotoxicity in a time-series aspect, SD rats were administrated once daily with saline, genamycin 80 mgkg for 28 consecutive days by intramuscular injection folled by 28 days recovery. Kidney samples were collected for microarray analysis and histological examination. There were 4360 and 4323 regulated genes for females and males, respectively, however, the overlapping expression genes coregluated at each time point were few, with 2 for females and 12 for males. By Principle Component Analysis and Hierarchical Cluster, the gene expression patterns were apparently associated with the disease stage of the nephrotoxicity,while GO Annotation showed the biological processes were specific to each course of this nephrotoxicity.Our studymapped the different gene expression patterns at the initiation, development and recovery stage of gentamycin-induced nephrotoxicity Gene expression in kidney from SD rats administrated once daily with saline or 80 mg/kg genamycin by intramuscular injection for 28 consecutive days follwed by 28 days recovery were measured using Aglient Rat Whole Genome 4*44 k array
Project description:Skin aging is a process of structural and compositional remolding that can be manifested as wrinkling and sagging. Remarkably, the dermis plays a dominant role in the process of skin aging. Recent studies suggest that microRNAs (miRNAs) may play a role in the regulation of gene expression in organism aging. However, studies about age-related miRNAs in human skin remain limited. In order to obtain an overall view of miRNAs expression in human aged dermis, we have investigated the alteration of microRNAs during aging by examining biopsies of human dermis from 12 young and aged donors, and demonstrated that numerous microRNAs showed significant alteration in dermis tissue. Normal human dermal tissue from 12 consenting individuals. Old group vs young group. Old group: with the age over 60 years old; young group: with the age below 10 years old; each group was constituted of 6 individuals.