Project description:RNA sequencing of sorted cell types, isolated from mice kidneys, after unilateral ureteral obstructive (UUO) surgery after 2 days, 7 days and a reversible (rUUO) 14 day model with corresponding sham operated mice. The goal of the study was to identify temporal gene expression changes in different cell types corresponding with kidney injury, in order to understand cell specific transcriptomic changes in the context of kidney injury and repair.
Project description:Small RNA sequencing of sorted cell type, mice kidneys, after unilateral ureteral obstructive (UUO) surgery after 2 days, 7 days and a reversible (rUUO) 14 day model with corresponding sham operated mice. The goal of the study is to identify micro-RNA dysregulation of expression between different cell types corresponding with kidney injury, in order to identify and assess biomarkers which could be translated into the clinical setting.
Project description:Tissue inhibitors of metalloproteinases (TIMP) are endogenous inhibitors of matrix metalloproteinases (MMP). While TIMP2 and TIMP3 inhibit MMPs, TIMP3 also inhibits activation of pro-MMP2 whereas TIMP2 promotes it. Here we assessed the differential role of TIMP2 and TIMP3 in renal injury using the unilateral ureteral obstruction model. Gene microarray assay showed that post-obstruction, the lack of TIMP3 had a greater impact on gene expression of intermediate, late injury- and repair-induced transcripts, kidney selective transcripts and solute carriers. Renal injury in TIMP3-/-, but not in TIMP2-/- mice increased expression of collagen type I/III, connective tissue growth factor, transforming growth factor-β and the downstream Smad2/3 pathway. Interestingly, ureteral obstruction markedly increased MMP2 activation in the kidneys of TIMP3-/- mice which was completely blocked in the kidneys of TIMP2-/- mice. These changes are consistent with enhanced renal tubulointerstitial fibrosis in TIMP3-/- and its reduction in TIMP2-/- mice. The activity of tumor necrosis factor-α converting enzyme, caspase-3 and mitogen activated kinases were elevated in the kidneys of TIMP3-/- but not TIMP2-/- mice, suggesting enhanced activation of apoptotic and pathological signaling pathways only in the obstructed kidney of TIMP3-/- mice. Thus, TIMP2 and TIMP3 play differential and contrasting roles in renal injury, TIMP3 protects from damage whereas TIMP2 promotes injury through MMP2 activation. Kidneys from the wild type (WT), TIMP2-/- and TIMP3-/- mice undergoing sham or unilateral ureteral obstruction (UUO) procedures
Project description:The mRNA transcriptome and m6A methylation microarray profiling of mouse kidney tissues. Kidney tissues from the sham-operated group and unilateral ureteral ligation/obstruction (UUO) kidney tissues were compared. The latter were mainly fibrotic kidney tissues. The goal was to identify the effect of the renal fibrosis on gene expression and corresponding m6A modifications during kidney fibrosis.
Project description:The mRNA transcriptome and m6A methylation microarray profiling of mouse kidney tissues. Kidney tissues from the sham-operated group and unilateral ureteral ligation/obstruction (UUO) kidney tissues were compared. The latter were mainly fibrotic kidney tissues. The goal was to identify the effect of the renal fibrosis on gene expression and corresponding m6A modifications during kidney fibrosis.