Project description:To better understand the molecular underpinnings of nephrogenesis at key developmental stages, we performed a bulk gene expression profiling in mouse kidneys at embryonic day 15.5 (E15.5) to identify genes essential for normal kidney development and to provide insights to the mechanisms underlying congenital anomalies of the kidney and urinary tract.
Project description:Transcriptome analysis of RNA samples from whole heart Transverse aortic constriction (TAC) is a well-established method for studying the pathomechanisms of heart failure in animal models of cardiac hypertrophy. A number of studies have shown that the treatment of heart failure in this animal model of cardiac hypertrophy suggests that hypertrophy and fibrosis may be reversible. However, since TAC-release protocols that improve hemodynamics by releasing physical stenosis remain undefined, the histological characteristics and molecular biological regulatory mechanisms of the reversibility of cardiac hypertrophy and fibrosis are unknown. Therefore, this study aimed to establish a TAC release model and investigate the reversibility and plasticity mechanisms of myocardial hypertrophy, fibrosis, and angiogenesis. Four weeks post-TAC surgery, TAC release was conducted by cutting the aortic stenosis sutures. The TAC group exhibited severe myocardial hypertrophy, fibrosis, and increased angiogenesis, along with diastolic dysfunction. Conversely, the TAC-release group showed reduced hypertrophy and fibrosis, and improved diastolic function. Gene expression analysis highlighted Regulator of Calcineurin 1 as a key player in cardiac function and histological changes post-TAC release. Rcan1 knockdown exacerbated myocardial hypertrophy and fibrosis in the TAC-release group. This study sheds light on the functional, structural, and histological changes in the heart induced by TAC release and elucidates some of its regulatory mechanisms.
Project description:Several lines of evidence indicate that there exists differential display of biochemical characteristics in endometrium during receptivity in the proven conception cycle as compared to corresponding secretory phases endometrium of non-conception cycles of fertile rhesus monkeys. In the present study, we examined the differential display in the whole genome expression of endometrium during days 2, 4 and 6 post-ovuation in proven conception cycles and normo-ovulatory, non-conception cycles in proven fertile rhesus monkeys. Female monkeys showing at least two consecutive ovulatory menstrual cycles of normal length were allocated to either of the two groups: group 1 in which females were allowed to cohabit with proven fertile males during days 8 to 16 of their menstrual cycles, and group 2 in which females were not allowed to cohabit. Vaginal smears were checked daily and the days of ovulation were assessed from immunopositive profiles of estradiol-17β and progesterone in peripheral serum samples. Endometrial samples were collected on days 2, 4 and 6 after ovulation from both groups of animals following laparotomy and fundal hysterectomy under ketamine anaesthesia. In group 1, only endometrial samples obtained from mated females who yielded viable, preimplantation-stage matched embyos on uterine flushing were used. In group 2, endometrial samples were obtained from females who showed normal ovulatory cycles. Tissue samples from both groups were washed in ice-cold PBS and were used for RNA extraction to run rhesus monkey whole genome expression array. On average, ~60% and ~68% genes of total number of hybridized genes were expressed in endometrial samples of groups 1 and 2, respectively. Group-wise hierarchical cluster analysis (HCA) yielded highest segregation between peri-implantation stage (groups 1b and 1c) and other (groups 2a-c and group 1a) samples with cluster distance (cd) 0.9, when cd=1.0 denotes complete segregation. On the other hand, least segregation was seen between groups 1a and 2a with cd 0.2, when cd=0 denotes complete aggregation. The number of common genes were less with the progress in days in group 1 (that is in proven conception cycle) unlike that in group 2 (that is in non-mated, normo-ovulatory group). Also, the number of common genes between groups for a given day after ovulation displayed a clear declining trend with increasing number of uncommon genes. Differential dipslay of regulated common genes among all the subgroups based on statistical analyses of variances in data sets obtained from whole genome expression arrays identified a total of fifteen (15) genes that displayed differential (>2-fold, p< 0.05) expression: ADCY5, ADIPOR1, AVEN, CHRND, FOXD3, GJD4, MAPK8IP3, MKS1, NNMT, NUP50, PALT1, PIGV, TGFBR2, TOX2, VWA5B1.
Project description:Microarray analysis of gene expression after transverse aortic constriction in mice: comparison of TAC vs. sham group at 48 hours, 10 days, and 3 weeks.