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Single cell RNA-seq on kidneys of mice with inactivated hepatocellular Mdm2.

ABSTRACT: In our study we aimed to characterise the effects of p53-induced liver senescence on murine kidneys. We induced liver senescence in 8-12 weeks old male mice by compromising hepatocellular Mdm2 functionality through systemic administration of the AAV8-TBG-Cre viral vector (ΔMdm2Hep mice). We observed transmision of the senescent phenotype from the senescent liver to the genetically unmanipulated kidney. To further elucidate the mechanisms that mediate this transmission phenotype and to characterise its effects on the kidney, we performed single-cell RNA sequencing (scRNA-seq) on the kidneys of 3 ΔMdm2Hep and 3 control mice. We observed the upregulation of several signalling pathways in specific renal cell compartments (e.g. TGFβ in the tubular compartment and JAK-STAT in the mesenchymal compartment). Our results show that liver senescence has a different effect on the renal transcriptome depending on the cellular compartment.

ORGANISM(S): Mus musculus

PROVIDER: GSE189726 | GEO | 2022/02/01

REPOSITORIES: GEO

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Plasminogen activator inhibitor-2 regulates immune response in kidney injury and renal aging mpact of plasminogen activator inhibitor-2 in kidney injury and renal aging

Project description:The plasminogen activator inhibitor-2 (PAI-2; encoded by the SerpinB2 gene) has been described in the context of macrophage activation and in cellular senescence. As both mechanisms are important in kidney disease we tested a possible role of PAI-2 in renal injury and repair. Methods:Aging, ischemia/reperfusion injury and unilateral ureteral obstruction were performed on the mice. Bone marrow was transplantefrom SerpinB2-/- to wild-type littermates and vice versa. Primary tubular cells and macrophages from SerpinB2-/- and wildtype mice were used for functional studies and transcriptional profiling. Results: PAI-2 expression was up-regulated in cultured senescent tubular cells and in kidneys of aged mice. In the lack of PAI-2 in SerpinB2-/- mice was associated with enhanced renal fibrosis and an inflammatory phenotype during aging and in kidney injury models. While acute injury was associated with fewer monocytes/macrophages in SerpinB2-/- kidneys the subsequent resolution of inflammation seen in wildtype kidneys was lacking in knockout mice. Conclusion: PAI-2 regulates renal aging, tubular damage, and resolution of inflammation. PAI-2 is crucial for kidney repair in mice .

2019-10-22 | GSE139156 | GEO

RNA-SEQ analysis of single cells extracted from the renal vesicles of Crym-EGFP transgenic post natal day 4 (P4) mice.

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Transcription profiling of human tumors vs. normal kidneys

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Molecular Basis of Renal Adaptation in a Murine Model of Congenital Obstructive Nephropathy

Project description:Congenital obstructive nephropathy is a common cause of chronic kidney disease and a leading indication for renal transplant in children. The cellular and molecular responses of the kidney to congenital obstruction are incompletely characterized. In this study, we evaluated global transcription in kidneys with graded hydronephrosis in the megabladder (mgb-/-) mouse to better understand the pathophysiology of congenital obstructive nephropathy. Three primary pathways associated with kidney remodeling/repair were induced in mgb-/- kidneys independent of the degree of hydronephrosis. These pathways included retinoid signaling, steroid hormone metabolism, and renal response to injury. Urothelial proliferation and the expression of genes with roles in the integrity and maintenance of the renal urothelium were selectively increased in mgb-/- kidneys. Ngal/Lcn2, a marker of acute kidney injury, was elevated in 36% of kidneys with higher grades of hydronephrosis. Evaluation of Ngalhigh versus Ngallow kidneys identified the expression of several novel candidate markers of renal injury. This study indicates that the development of progressive hydronephrosis in mgb-/- mice results in renal adaptation that includes significant changes in the morphology and potential functionality of the renal urothelium. These observations will permit the development of novel biomarkers and therapeutic approaches to progressive renal injury in the context of congenital obstruction. Gene expression was measured in control, mild, moderate and severely hydronephrotic megabladder mouse kidneys. A total of 6 control kidneys were compared to 18 mutant kidneys from age-matched male animals.

2013-06-18 | E-GEOD-48041 | biostudies-arrayexpress

Molecular Basis of Renal Adaptation in a Murine Model of Congenital Obstructive Nephropathy

2013-06-18 | GSE48041 | GEO

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2013-02-10 | E-GEOD-38117 | biostudies-arrayexpress

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