Project description:CyTOF data showed that 3-HAA significantly increased the percentage of F4/80hiCX3CR1loKi67loMHCIIhi macrophage and decreased the percentage of F4/80loCD64+PD-L1lo macrophages. scRNA-seq analyses demonstrated that 3-HAA administration was proved to regulate the function of M1 macrophages, M2 macrophages, and proliferating macrophages.
Project description:To clarify the mechanisms of cyclophosphamide (CY)-induced myocardial damage, we have analyzed the genome-wide expression profiles of C57BL/6J mice received CY, one of CY metabolites acrolein, and CY with N-acetyl cysteine (NAC). The microarray analysis revealed that the gene expression of L-type calcium channel (DHPR), ryanodine receptor 2 (RyR2), and Troponin C (TnC) were suppressed by CY administration. DHPR, RyR2 and TnC are responsible for control of intracellular calcium ion concentration and important for myocardial contraction. On the other side, the gene expression profiles after administration of acrolein differed from CY administration. Furthermore, the gene expression profiles after administration of NAC and CY, NAC did not inhibit the DHPR, RyR2 and TnC gene expression suppression.
Project description:Han:SPRD Cy is a spontaneous rat model of polycystic kidney disease (PKD) caused by a missense mutation in Pkdr1. Cystogenesis in this model is not clearly understood. In the current study, we performed global gene expression profiling in early-stage PKD cyst development in Cy/Cy kidneys and normal (+/+) kidneys, at 3 and 7 days of postnatal age. Expression profiles were determined by microarray analysis, followed by validation with real-time RT-PCR. Genes were selected with over 1.5 fold expression changes compared with age-matched +/+ kidneys for canonical pathway analysis. We found 9 pathways in common between 3-day and 7-day Cy/Cy kidneys. Three significantly changed pathways were designated 'VDR/RXR Activation,' 'LPS/IL-1 Mediated Inhibition of RXR Function,' and 'LXR/RXR Activation'. These results suggest that RXR mediated signaling is significantly altered in developing kidneys with mutated Pkdr1. In gene ontology analysis, the functions of these RXR-related genes were found to be involved in regulating cell proliferation and organ morphogenesis. With real-time RT-PCR analysis, the up-regulation of Ptx2, Alox15b, OSP and PCNA, major markers of cell proliferation associated with the RXR pathway, were confirmed in 3- and 7-day Cy/Cy kidneys compared with 3-day +/+ kidneys. The increased RXR protein was observed both in nuclei and cytoplasm of cystic epithelial cells in early-stage Cy/Cy kidneys, and the RXR-positive cells were strongly positive for PCNA staining. Taken together, cell proliferation and organ morphogenesis signals transduced by RXR mediated pathways may have important roles for cystogenesis in early-stage PKD in this Pkdr1-mutated Cy rat.