Role of Chromogranin A on renal function in a mouse model of failing kidney
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PROVIDER: PRJNA416147 | ENA |
REPOSITORIES: ENA
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Project description:Chromogranin A (CHGA) is elevated in plasma of patients with renal failure and several CHGA polymorphisms are associated with hypertensive renal disease. Therefore, we investigated the role of CHGA in kidney disease using the partial nephrectomy model of kidney failure. Mice under surgery to remove 2/3rds of the left kidney and the entire right kidney. Control mice received the sham surgery. Wild-type and CHGA-/- mice used. To model the changes in vitro, CRL-1927 kidney cells were treated with or without CHGA in vitro.
2018-10-25 | GSE106300 | GEO
Project description:Kidney fibrosis an important determinant of clinical outcomes in individuals with chronic kidney disease (CKD). The stoichiometric ratio of collagens in renal scar tissue differs from that of ECM of healthy kidneys but the functional importance of altered collagen types injured kidneys remains unclear. Using population studies and multiple independent clinical datasets, we show that circulating protein and renal mRNA amounts of Col5a1 exhibited associations with kidney disease and incident CKD risk. Using murine models of tubulo-interstitial kidney injury, we show that Col V regulates the degree of post injury fibrosis and renal function. We demonstrated that mice with conditionally knocked out Col5a1 (Col5a1CKO ) exhibited decreased renal function and greater renal fibrosis after kidney injury . Renal fibroblasts in Col5a1CKO animals upregulated vβ3 integrin. Inhibition of vβ3 signaling with a small molecule, cilengitide, rescued post-injury renal function in Col5a1 CKO animals. Using the hybrid mouse diversity panel (HMDP) that comprises 100 diverse inbred strains of mice, we observed that the ratio of expression of Col5a1 after injury compared to healthy animals exhibited genetic variation . Strains with low Col5a1 ratios exhibited worse renal function compared to animals that had higher ratios . Col5a1 expression in peripheral blood mononuclear cells after injury compared to uninjured animals to identify Col5a1-non responder strains, we demonstrate that cilengitide can significan tly rescue kidney function in non-responder strains . Overall we found that Col V regulates renal function and fibrosis after kidney injury. These data suggest the feasibility of precision medicine approaches for targeting pathways downstream of Col5a1 to promote kidney repair.
2025-03-17 | GSE290664 | GEO
Project description:Kidney fibrosis an important determinant of clinical outcomes in individuals with chronic kidney disease (CKD). The stoichiometric ratio of collagens in renal scar tissue differs from that of ECM of healthy kidneys but the functional importance of altered collagen types injured kidneys remains unclear. Using population studies and multiple independent clinical datasets, we show that circulating protein and renal mRNA amounts of Col5a1 exhibited associations with kidney disease and incident CKD risk. Using murine models of tubulo-interstitial kidney injury, we show that Col V regulates the degree of post injury fibrosis and renal function. We demonstrated that mice with conditionally knocked out Col5a1 (Col5a1CKO ) exhibited decreased renal function and greater renal fibrosis after kidney injury . Renal fibroblasts in Col5a1CKO animals upregulated vβ3 integrin. Inhibition of vβ3 signaling with a small molecule, cilengitide, rescued post-injury renal function in Col5a1 CKO animals. Using the hybrid mouse diversity panel (HMDP) that comprises 100 diverse inbred strains of mice, we observed that the ratio of expression of Col5a1 after injury compared to healthy animals exhibited genetic variation . Strains with low Col5a1 ratios exhibited worse renal function compared to animals that had higher ratios . Col5a1 expression in peripheral blood mononuclear cells after injury compared to uninjured animals to identify Col5a1-non responder strains, we demonstrate that cilengitide can significan tly rescue kidney function in non-responder strains . Overall we found that Col V regulates renal function and fibrosis after kidney injury. These data suggest the feasibility of precision medicine approaches for targeting pathways downstream of Col5a1 to promote kidney repair.
2025-03-17 | GSE290663 | GEO
Project description:The number of heart failure (HF) patients is increasing. HF is frequently accompanied by kidney dysfunction and such organ failure is closely related. Recent investigations revealed that increased renal venous pressure, rather than decreased cardiac output, causes the deterioration of kidney function in HF patients; however, the underlying responsible mechanisms are unknown. We demonstrated that reduced blood flow speed in peritubular capillaries (PTCs) by renal congestion and upregulation of nuclear factor-κB (NF-κB) signaling synergistically exacerbate kidney injury. We generated a novel mouse model with unilateral renal congestion by coarctation of the inferior vena cava between renal veins. Intravital imaging highlighted the notable dilatation of PTCs and decreased renal blood flow speed in the congestive kidney. Renal damage after ischemia reperfusion injury was exacerbated in the congestive kidney and accumulation of polymorphonuclear leukocytes (PMNs) within PTCs was observed at the acute phase after injury. Pharmacological inhibition of NF-κB ameliorated renal congestion-mediated exacerbation of kidney injury. In vitro, adhesion of PMNs on the TNFα-stimulated endothelial cells was accelerated by perfusion of PMNs at a slower speed, which was cancelled by the inhibition of NF-κB signaling. Our study demonstrates the importance of slower blood flow accompanying activated NF-κB signaling in the congestive kidney in the exacerbation of renal injury. These mechanisms may explain how increased renal venous pressure in HF patients causes the deterioration of kidney dysfunction. Inhibition of NF-κB signaling may be a therapeutic candidate for the vicious cycle between heart and kidney failure with increased renal venous pressure.
2024-02-16 | GSE166838 | GEO
Project description:The study comprises various components: Samples TD: We aims to screen out different gene expression profile in donor biopsies after revascularization , We aims to predict renal allograft dysfunction early after transplantation. Samples AR, ATN, Tx: We aim to screen out different gene expression profile in acute rejection on the kidney. We aim to screen out different gene expression profile in acute tubular necrosis on the kidney. Results from the various study components can help to diagnose renal allograft dysfunction with different causes by distinct gene expression profile. Keywords: acute rejection, acute tubular necrosis, donor biopsies, renal allograft dysfunction Samples AR1-AR17: This study has been accomplished with 17 patients of acute rejection on the kidney.Technical replicates: 2 replicates Samples ATN1-ATN5: This study has been accomplished with 5 patients of acute tubular necrosis on the kidney. Technical replicates: 2 replicates Samples Tx1-Tx14: This study has been accomplished with 14 patients of stable renal function on the kidney.Tecnical replicates:2 replicates(except Tx12) Samples TD1-TD12: This study has been accomplished with 12 patients of donor tissue with stable function early after transplantation on the kidney.Technical replicates: 2 replicates Samples TD13-TD21: This study has been accomplished with 9 patients of donor tissue with renal dysfunction early after transplantation on the kidney.Technical replicates: 2 replicates
2011-02-02 | E-GEOD-26578 | biostudies-arrayexpress
Project description:Renal gluconeogenesis accounts for half of systemic gluconeogenesis during starvation, but its regulatory mechanisms and implications in chronic kidney disease (CKD) remain unknown. In this study, using single-cell RNA sequencing of starved kidneys and various animal models, we aimed to identify key pathways involved in renal gluconeogenesis and their role in the development of hypoglycemia during starvation in diseased kidneys. Under the starvation condition, renal gluconeogenesis was highly induced in proximal tubule cells with FOXO1 activation. In renal tubular epithelial cells, starvation-induced FOXO1 activation was required to stimulate gluconeogenesis and promote glucose production. We further analyzed whether renal FOXO1-mediated gluconeogenesis is impaired in CKD. In CKD animal models, the kidneys exhibited reduced FOXO1 and gluconeogenic protein expression; however, serum glucose levels remained unchanged, suggesting that diminished renal gluconeogenesis does not significantly impact circulating glucose levels. When CKD mice were subjected to starvation, serum glucose levels were significantly reduced after 72 hours. In the CKD model, FOXO1 activation failed, accompanied by a lower induction of gluconeogenic protein expression. Similar to diseased condition, aged mice exposed to starvation also showed impaired gluconeogenic response in the kidney, contributing to reduced circulating glucose levels. Under the in vitro condition, we found that profibrotic TGFβ1 inhibits starvation-induced gluconeogenesis by directly suppressing the FOXO1 signaling pathway in tubular cells. Finally, we generated tubule-specific FOXO1 knockout (KO) mice by crossing FOXO1 floxed mice with Ksp-cre mice. These tubule-specific FOXO1 KO mice exhibited reduced expression of gluconeogenic genes in the kidney, leading to hypoglycemia during starvation. Collectively, we demonstrated crucial role of renal FOXO1 in gluconeogenesis during starvation, and its implication in kidney disease.
2025-06-30 | GSE293540 | GEO
Project description:Kidney transplantation restores renal function in patients with end-stage renal disease, yet long-term graft failure remains common and is often driven by immune dysregulation. We performed droplet-based single-cell RNA sequencing (10x Genomics 3′ v3 chemistry) on peripheral-blood mononuclear cells (PBMCs) collected from adult kidney-transplant recipients who either maintained stable renal function (Ctrl, n = 10) or displayed biopsy-proven graft dysfunction (PTRI, n = 10).
2025-07-02 | GSE298312 | GEO
Project description:The study comprises various components: Samples TD: We aims to screen out different gene expression profile in donor biopsies after revascularization , We aims to predict renal allograft dysfunction early after transplantation. Samples AR, ATN, Tx: We aim to screen out different gene expression profile in acute rejection on the kidney. We aim to screen out different gene expression profile in acute tubular necrosis on the kidney. Results from the various study components can help to diagnose renal allograft dysfunction with different causes by distinct gene expression profile. Keywords: acute rejection, acute tubular necrosis, donor biopsies, renal allograft dysfunction
2011-02-02 | GSE26578 | GEO
Project description:Direct comparison of FACS sorted EGFP positive renal macrophages vs pooled Total Kidney extract Keywords: Direct pairwise comparison
2007-07-04 | GSE6261 | GEO
Project description:Cycles of a fasting-mimicking diet (FMD) promote regeneration and reduce damage in the pancreas, blood, gut, and nervous systems of mice but its effect on kidney disease is unknown, and the FMD has not been tested in rats. Here we show that cycles of a newly developed low-salt FMD (LS-FMD) restore normal proteinuria, nephron structure and function in rats with puromycin-induced nephrosis in the long term. LS-FMD induces expression of nephrogenic markers, resembling renal developmental processes in multiple kidney structures, and activates podocyte-lineage reprogramming pathways, in addition to promoting a quiescent state in mature podocytes. In a pilot randomized cross-over study in patients with chronic kidney disease, FMD cycles promote renoprotection by reducing proteinuria and improving endothelial function. These results show that LS-FMD cycles, which promote the reprogramming of multiple renal cell types, leading to glomerular damage reversal, should be tested further in the treatment of progressive kidney diseases.
2025-07-30 | GSE240658 | GEO