Project description:The kidney is a complex organ that governs many physiological parameters. It is roughly divided into three parts, the renal pelvis, medulla, and cortex. Covering the cortex is the renal capsule, a serosal tissue that provides protection and forms a barrier for the kidney. Serosal tissues of many organs have been recently shown to play a vital role in homeostasis and disease. Analyses of the cells that reside in these tissues have identified distinct cell types with unique phenotypes. Surprisingly, despite the importance of serosal tissues, little is known about cells of the renal capsule. Here, we characterized this niche and found that it is mainly comprised of fibroblasts and macrophages, but also includes many other diverse cell types. Characterizing renal capsule- associated macrophages, we found that they consist of a distinct subset (i.e., TLF+ macrophages) that is nearly absent in the kidney parenchyma. Injury, disease, and other changes within the kidney, affected the cell composition and phenotype of the renal capsule, indicating its dynamic and vibrant response to changes within the organ parenchyma. Lastly, we studied age-related changes in the renal capsule and found that aging affected the cell composition and pro- inflammatory phenotype of macrophages, increased CD8 T cells and other lymphocyte counts, and promoted a senescence-associated phenotype in fibroblasts. Taken together, our data illustrate the complexity and heterogeneity of the renal capsule and its underlying changes during aging and disease, improving our understanding of the kidney serosa that may be valuable for novel renal therapies.
Project description:The kidney is a complex organ that governs many physiological parameters. It is roughly divided into three parts, the renal pelvis, medulla, and cortex. Covering the cortex is the renal capsule, a serosal tissue that provides protection and forms a barrier for the kidney. Serosal tissues of many organs have been recently shown to play a vital role in homeostasis and disease. Analyses of the cells that reside in these tissues have identified distinct cell types with unique phenotypes. Surprisingly, despite the importance of serosal tissues, little is known about cells of the renal capsule. Here, we characterized this niche and found that it is mainly comprised of fibroblasts and macrophages, but also includes many other diverse cell types. Characterizing renal capsule- associated macrophages, we found that they consist of a distinct subset (i.e., TLF+ macrophages) that is nearly absent in the kidney parenchyma. Injury, disease, and other changes within the kidney, affected the cell composition and phenotype of the renal capsule, indicating its dynamic and vibrant response to changes within the organ parenchyma. Lastly, we studied age-related changes in the renal capsule and found that aging affected the cell composition and pro- inflammatory phenotype of macrophages, increased CD8 T cells and other lymphocyte counts, and promoted a senescence-associated phenotype in fibroblasts. Taken together, our data illustrate the complexity and heterogeneity of the renal capsule and its underlying changes during aging and disease, improving our understanding of the kidney serosa that may be valuable for novel renal therapies.
Project description:We have generated a transgenic rat model with postnatal pathology. In order to investigate the potential contribution of changes in kidney gene expression to the pathology, we have conducted microarray-based gene expression profiling of postnatal kidney.
Project description:Temporal changes of gene expression from 1-wk- to 5-wk-old rat in kidney and lung, and the effect of prior growth inhibition on these genetic changes. In mammals, body growth is rapid in early life but decelerates with age. Somatic growth deceleration is caused by a gradual decline in cell proliferation that occurs simultaneously in many different organs, but is not caused by a hormonal mechanism. We hypothesize that growth deceleration is driven by a postnatal genetic program that occurs coordinately in multiple organs. Using microarrays, we investigated the changes of gene expression that occur with age in kidney and lung as growth slows down, and also investigated whether these changes were growth-driven, by asking whether prior delay of postnatal growth caused by malnutrition (tryptophan deficiency) would also delay these genetic changes.
Project description:Temporal changes of gene expression from 1-wk- to 5-wk-old rat in kidney and lung, and the effect of prior growth inhibition on these genetic changes. In mammals, body growth is rapid in early life but decelerates with age. Somatic growth deceleration is caused by a gradual decline in cell proliferation that occurs simultaneously in many different organs, but is not caused by a hormonal mechanism. We hypothesize that growth deceleration is driven by a postnatal genetic program that occurs coordinately in multiple organs. Using microarrays, we investigated the changes of gene expression that occur with age in kidney and lung as growth slows down, and also investigated whether these changes were growth-driven, by asking whether prior delay of postnatal growth caused by malnutrition (tryptophan deficiency) would also delay these genetic changes. To compare gene expression between fast-growing animals and more slowly growing animals, we extracted total mRNA from kidney and lung in 1-wk-old and 5-wk-old mice (5 animals each). Then, to investigate the effect of prior growth on these genetic changes, we also extracted total mRNA from kidney and lung in 5-wk-old mice that received a tryptophan-deficient diet from birth to 4wk of age.
Project description:We have generated a transgenic rat model with postnatal pathology. In order to investigate the potential contribution of changes in kidney gene expression to the pathology, we have conducted microarray-based gene expression profiling of postnatal kidney. Rat kidneys were sampled at mid-day of postnatal day 6 for RNA extraction and hybridization to Affymetrix Genechip arrays. Two biological replicates of both wild-type and transgenic kidneys were included in the study.
Project description:This SuperSeries is composed of the following subset Series: GSE14666: Expression data from female rat kidney: pathophysiology of proteinuria GSE14676: Expression data from male rat kidney: pathophysiology of proteinuria Refer to individual Series
Project description:To study in vivo action of Songling Xuemaikang Capsule (SXC), SHRs were orally administration with high- or low-dose of SXC for 28 days.Valsartan, an angiotensin receptor antagonist, is used as a positive control drug in this study and orally administrated for 28 days. The levels of AngII, Aldosterone in serum of SHRs from different groups were analyzed, and gene expression profiling were performed in the thoracic aortakidney of SHRs, using the Whole Rat Genome Oligonucleotide Microarray. The integrated causal network analysis is performed to understand the mechanism of antihypertensive effect of SXC. The results showed that expression of 706 unique genes (p<0.05) were changed (fold change >2.0) in SHRs at a dose of 472.5 mg/kg day SXC when compared with control rats, whereas the expression of 920 unique genes were changed (fold change>2.0) at a dose of 1417.5 mg/kg/day. Those genes are involved in lipid metabolism, complement system induced immune response, inflammation and vascular and endothelial dysfunction.