Project description:ICR-derived glomerulonephritis (ICGN) mice is a novel inbred strain of mice with a hereditary nephrotic syndrome. Deletion mutation of tensin 2 (Tns2), a focal adhesion molecule, has been suggested to be responsible for nephrotic syndrome in ICGN mice, however, existence of other associative factors has been suggested. To identify additional associative factors and to better understand onset mechanism of nephrotic syndrome in ICGN mice, comprehensive gene expression analysis using DNA microarray was conducted. Immune-related pathways were markedly altered in ICGN mice kidney as compared with ICR mice. Furthermore, gene expression level of complement component 1, s subcomponent (C1s), whose human homologue has been reported to associate with lupus nephritis, was markedly low in ICGN mice kidney. RNA from renal cortex of 4- and 8-week-old ICGN and ICR mice was extracted and processed for hybridization on Affymetrix microarrays (N=3).
Project description:ICR-derived glomerulonephritis (ICGN) mice is a novel inbred strain of mice with a hereditary nephrotic syndrome. Deletion mutation of tensin 2 (Tns2), a focal adhesion molecule, has been suggested to be responsible for nephrotic syndrome in ICGN mice, however, existence of other associative factors has been suggested. To identify additional associative factors and to better understand onset mechanism of nephrotic syndrome in ICGN mice, comprehensive gene expression analysis using DNA microarray was conducted. Immune-related pathways were markedly altered in ICGN mice kidney as compared with ICR mice. Furthermore, gene expression level of complement component 1, s subcomponent (C1s), whose human homologue has been reported to associate with lupus nephritis, was markedly low in ICGN mice kidney.
Project description:The responsive and abundant lncRNAs to pro-inflammatory factors in human ECs were screened and validated by RNA sequencing and qPCR. ICAM1-related non-coding RNA (ICR) was identified as the most potential candidate. In vivo data confirmed ICR was upregulated in atherosclerotic plaque. Knock down and overexpression experiments showed that ICR plays an essential role for EC adhesion and migration as well as for the expression of its adjacent ICAM1 gene. Mechanistically, we unexpectedly found in quiescent ECs, ICR regulates mRNA stabilization of ICAM1 through a RNA duplex formation mechanism while in activated ECs, ICR modulated ICAM1 transcription via a NF-κB-dependent manner. RNA-seq and PCR analysis demonstrated a vast number of pro-inflammatory genes downstream of NF-κB were regulated by ICR. Further, CHIP assay showed p65 directly binds to ICR promoter and facilitate the transcription. Interestingly, we found p65 phosphorylation and degradation was in turn regulated by ICR, forming a feedback activation of NF-κB signaling. Finally, we screened siRNA of mouse ICR and delivered the shRNA adenovirus by intravenous injection in a high fat diet induced ApoE-/- atherosclerosis model, it was found that both aortic root stenosis and plaque area could be markedly inhibited by suppressing ICR.
Project description:We profiled a RNA-seq on ICR mouse testis. We found that AOS can improve the expression of the genes important for spermatogenesis in the cultured testis.
