The aging kidney is characterized by tubuloinflammaging, a phenotype associated with MHC-II gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE233718 | GEO | 2023/09/11
REPOSITORIES: GEO
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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
Project description:IntroductionEven during physiologic aging, the kidney experiences a loss of mass and a progressive functional decline. This is clinically relevant as it leads to an increased risk of acute and chronic kidney disease. The kidney tubular system plays an important role in the underlying aging process, but the involved cellular mechanisms remain largely elusive.MethodsKidneys of 3-, 12- and 24-month-old male C57BL/6J mice were used for RNA sequencing, histological examination, immunostaining and RNA-in-situ-hybridization. Single cell RNA sequencing data of differentially aged murine and human kidneys was analyzed to identify age-dependent expression patterns in tubular epithelial cells. Senescent and non-senescent primary tubular epithelial cells from mouse kidney were used for in vitro experiments.ResultsDuring normal kidney aging, tubular cells adopt an inflammatory phenotype, characterized by the expression of MHC class II related genes. In our analysis of bulk and single cell transcriptional data we found that subsets of tubular cells show an age-related expression of Cd74, H2-Eb1 and H2-Ab1 in mice and CD74, HLA-DQB1 and HLADRB1 in humans. Expression of MHC class II related genes was associated with a phenotype of tubular cell senescence, and the selective elimination of senescent cells reversed the phenotype. Exposure to the Cd74 ligand MIF promoted a prosenescent phenotype in tubular cell cultures.DiscussionTogether, these data suggest that during normal renal aging tubular cells activate a program of 'tubuloinflammaging', which might contribute to age-related phenotypical changes and to increased disease susceptibility.
| S-EPMC10477980 | biostudies-literature
Project description:CD24, or heat stable antigen, is a cell surface sialoglycoprotein expressed on immature cells that disappears after the cells have reached their final differentiation stage. CD24 may be important in human embryonic kidney epithelial cell differentiation. In mice, CD24 expression is up-regulated in the early metanephros and localized to developing epithelial structures but the role and expression of CD24 in the developing human kidney has not been well described. In normal human fetal kidneys from 8 to 38 weeks gestation, CD24 expression was up-regulated and restricted to the early epithelial aggregates of the metanephric blastema and to the committed proliferating tubular epithelia of the S-shape nephron; however individual CD24+ cells were identified in the interstitium of later gestation and postnatal kidneys. In freshly isolated cells, FACS analysis demonstrated distinct CD24+ and CD24+133+ cell populations, constituting up to 16% and 14% respectively of the total cells analyzed. Isolated and expanded CD24+ clones displayed features of an epithelial progenitor cell line. Early fetal urinary tract obstruction resulted in an upregulation of CD24 expression, both in developing epithelial structures of early gestation kidneys and in the cells of the injured tubular epithelium of the later gestation kidneys. These results highlight the cell specific expression of CD24 in the developing human kidney and dysregulation in fetal urinary tract obstruction. We used microarrays to define the differences in global gene expression between obstructed and normal human fetal kidneys. We analyzed RNA extracted from human fetal kidneys between the gestational ages 8 and 18 weeks gestation. This dataset is part of the TransQST collection.
2009-11-11 | E-GEOD-18969 | biostudies-arrayexpress
Project description:To investigated the functional characteristics and molecular mechanisms underlying senescence in UV irradiated melanocytes. We performed gene expression profiling analysis using data obtained from scRNA-seq of UV-irradiated senescent melanocytes.
2023-04-03 | GSE228471 | GEO
Project description:To investigated the functional characteristics and molecular mechanisms underlying senescence in UV irradiated melanocytes. We performed gene expression profiling analysis using data obtained from RNA-seq of 3 normal melanocytes and 3 UV-irradiated senescent melanocytes.
2023-04-03 | GSE228470 | GEO
Project description:To compare the transcriptional profile in aged kidneys lacking tubular Cpt1a with floxed littermate controls.
2024-03-01 | GSE205497 | GEO
Project description:The Hippo/YAP pathway plays a critical role in early embryonic kidney development, but its functions in the adult kidney are less well understood. Our previous work has demonstrated that tubular YAP activation induced by double knockout of the upstream Hippo kinases Mst1 and Mst2 (Mst1/2 dKO) promotes tubular injury and renal inflammation under basal conditions. However, the importance of tubular YAP activation remains to be established in injured kidneys in which many other injurious pathways are simultaneously activated. Several secreted factors were found to be increased by YAP in tubular cells, but how the transcriptional network is altered by YAP is largely unknown. Here, we show that tubular YAP was already activated at 6 h after unilateral ureteral obstruction (UUO). Tubular YAP deficiency greatly attenuated tubular cell over-proliferation, tubular injury and renal inflammation induced by UUO or cisplatin. RNA-Seq, ChIP and luciferase assay revealed that YAP promoted the transcription of the transcription factor KLF5 whereas no interaction between YAP and KLF5 was observed. Consistently, the elevated expression of KLF5 and its target genes in Mst1/2 dKO or UUO kidneys was blocked by ablation of Yap in tubular cells. Inhibition of KLF5 prevented tubular cell over-proliferation, tubular injury and renal inflammation in Mst1/2 dKO kidneys. Therefore, our results demonstrate that tubular YAP is a key player in kidney injury. YAP and KLF5 form a transcriptional cascade, in which tubular YAP activation induced by kidney injury promotes KLF5 transcription. Activation of this cascade induces tubular cell over-proliferation, tubular injury and renal inflammation
2024-05-01 | GSE235443 | GEO
Project description:Role of Tubular Cpt1a in Aging Murine Kidneys
| PRJNA846071 | ENA
Project description:Glomerular and tubulointerstitial fractions were enriched from human kidneys samples. Ages of human kidney samples: 15, 29, 37, 61, 67 and 69 years of age. The glomerular and tubulointerstitial samples were processed to enrich for extracellular matrix components and the fractions analysed by mass spectrometry.
2022-02-22 | PXD022219 | Pride
Project description:Although the tubule is the epicenter of damage, kidney fibroblast is increasingly appreciated in governing the prognosis of acute kidney injury (AKI). Smoothened (Smo), a heptahelical transmembrane protein, carries a hedgehog signal to mediate the communications between kidney fibroblasts and tubular epithelium through an undetermined mechanism in AKI. Integrating in vivo, ex vivo, and in vitro approaches with systems biology, we report that Smo-specific ablation in fibroblast preserved kidney function and mitigated tubular cell apoptosis or inflammation after AKI. Loss of Smo in fibroblasts enhanced the activity of perivascular mesenchymal cells. Global proteomics revealed extracellular matrix is a key cellular compartment where significant proteins are distributed, and Nidogen-1 is a prominent basement membrane glycoprotein highly expressed in fibroblast-Smo specific ablation kidneys. Co-immunoprecipitation showed that Smo binds Nidogen-1. Phosphoproteomics identified wnt signaling pathway, the AKI protector, was activated in fibroblast Smo deletion kidneys. In vitro and ex vivo, Nidogen-1 induced wnts and repressed tubular cell apoptosis. Our results suggest that fibroblast-derived Smo dictates AKI fate through cell-matrix-cell interactions and provides open-access data resources to understand AKI pathogenesis better.
2021-12-23 | MSV000088609 | MassIVE