Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Parabiosis and single-cell RNA-Sequencing reveal a limited contribution of monocytes to myofibroblasts in kidney fibrosis

ABSTRACT: Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells including mesenchymal stem cells, macrophages and fibrocytes to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium we confirm that proximal tubule does not contribute to the myofibroblast pool. However, in parabiosis models in which one parabiont is genetically labeled and the other is unlabeled and undergoes kidney fibrosis, we demonstrate that a small fraction of genetically labeled renal myofibroblasts derive from the circulation. Single cell RNA-Sequencing confirms this finding but indicates that these cells are circulating monocytes, express few extracellular matrix or other myofibroblast genes and do express many proinflammatory cytokines. We conclude that this small circulating myofibroblast progenitor population contributes to renal fibrosis by paracrine rather than direct mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE112033 | GEO | 2018/04/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

miR-132 mediates renal fibrosis: Genome-wide analysis of gene expression in foxd1-derivative interstital cells derived from fibrotic kidneys from mice treated with antagomir-132 or scramblemir

Project description:Chronic kidney disease is associated with progressive renal fibrosis, where perivascular cells give rise to the majority of Î±-SMA positive myofibroblasts. We sought to identify pericytic miRNAs that could serve as a target to decrease myofibroblast formation. We induced kidney fibrosis in FoxD1-GC;Z/Red-mice by unilateral ureteral obstruction (UUO) followed by FACS sorting of dsRed-positive FoxD1-derivative cells and miRNA profiling. MiR-132 selectively increased 21-fold during pericyte-to-myofibroblast formation whereas miR-132 was only 2.5-fold up in total kidney lysates (both in UUO and ischemia-reperfusion injury). MiR-132 silencing in UUO decreased collagen deposition (35%) and tubular apoptosis. Immunohistochemistry, western blot and qRT-PCR confirmed a similar decrease in interstitial Î±-SMA+ cells. Pathway analysis identified a rate-limiting role for miR-132 in myofibroblast proliferation that was confirmed in vitro. Indeed, antagomir-132 treated mice displayed a reduction in the number of proliferating, ki67+ interstitial myofibroblasts. Interestingly, this was selective for the interstitial compartment and did not impair the reparative proliferation of tubular epithelial cells, as evidenced by an increase in ki67+ epithelial cells, as well as increased (p-)RB1, Cyclin-A and decreased RASA1, p21 levels in kidney lysates. Taken together, silencing miR-132 counteracts the progression of renal fibrosis by selectively decreasing myofibroblast proliferation and could potentially serve as a novel antifibrotic therapy. Total RNA obtained from FACS sorted mouse renal FoxD1-derivatve interstitial cells from mice that were treated with antagomir-132 or scramblemir and underwent UUO (n=4)

2016-02-16 | E-GEOD-76548 | biostudies-arrayexpress

miR-132 mediates renal fibrosis: miRNA profiling of foxd1-derivative interstital cells derived from murine fibrotic kidneys compared to healthy kidneys

Project description:Chronic kidney disease is associated with progressive renal fibrosis, where perivascular cells give rise to the majority of Î±-SMA positive myofibroblasts. We sought to identify pericytic miRNAs that could serve as a target to decrease myofibroblast formation. We induced kidney fibrosis in FoxD1-GC;Z/Red-mice by unilateral ureteral obstruction (UUO) followed by FACS sorting of dsRed-positive FoxD1-derivative cells and miRNA profiling. MiR-132 selectively increased 21-fold during pericyte-to-myofibroblast formation whereas miR-132 was only 2.5-fold up in total kidney lysates (both in UUO and ischemia-reperfusion injury). MiR-132 silencing in UUO decreased collagen deposition (35%) and tubular apoptosis. Immunohistochemistry, western blot and qRT-PCR confirmed a similar decrease in interstitial Î±-SMA+ cells. Pathway analysis identified a rate-limiting role for miR-132 in myofibroblast proliferation that was confirmed in vitro. Indeed, antagomir-132 treated mice displayed a reduction in the number of proliferating, ki67+ interstitial myofibroblasts. Interestingly, this was selective for the interstitial compartment and did not impair the reparative proliferation of tubular epithelial cells, as evidenced by an increase in ki67+ epithelial cells, as well as increased (p-)RB1, Cyclin-A and decreased RASA1, p21 levels in kidney lysates. Taken together, silencing miR-132 counteracts the progression of renal fibrosis by selectively decreasing myofibroblast proliferation and could potentially serve as a novel antifibrotic therapy. Total RNA obtained from FACS sorted mouse FoxD1-derivative interstitial cells from healthy or fibrotic kidneys

2016-02-16 | E-GEOD-76549 | biostudies-arrayexpress

miR-132 mediates renal fibrosis: miRNA profiling of foxd1-derivative interstital cells derived from murine fibrotic kidneys compared to healthy kidneys

Project description:Chronic kidney disease is associated with progressive renal fibrosis, where perivascular cells give rise to the majority of α-SMA positive myofibroblasts. We sought to identify pericytic miRNAs that could serve as a target to decrease myofibroblast formation. We induced kidney fibrosis in FoxD1-GC;Z/Red-mice by unilateral ureteral obstruction (UUO) followed by FACS sorting of dsRed-positive FoxD1-derivative cells and miRNA profiling. MiR-132 selectively increased 21-fold during pericyte-to-myofibroblast formation whereas miR-132 was only 2.5-fold up in total kidney lysates (both in UUO and ischemia-reperfusion injury). MiR-132 silencing in UUO decreased collagen deposition (35%) and tubular apoptosis. Immunohistochemistry, western blot and qRT-PCR confirmed a similar decrease in interstitial α-SMA+ cells. Pathway analysis identified a rate-limiting role for miR-132 in myofibroblast proliferation that was confirmed in vitro. Indeed, antagomir-132 treated mice displayed a reduction in the number of proliferating, ki67+ interstitial myofibroblasts. Interestingly, this was selective for the interstitial compartment and did not impair the reparative proliferation of tubular epithelial cells, as evidenced by an increase in ki67+ epithelial cells, as well as increased (p-)RB1, Cyclin-A and decreased RASA1, p21 levels in kidney lysates. Taken together, silencing miR-132 counteracts the progression of renal fibrosis by selectively decreasing myofibroblast proliferation and could potentially serve as a novel antifibrotic therapy.

2016-02-16 | GSE76549 | GEO

miR-132 mediates renal fibrosis: Genome-wide analysis of gene expression in foxd1-derivative interstital cells derived from fibrotic kidneys from mice treated with antagomir-132 or scramblemir

2016-02-16 | GSE76548 | GEO

PFKFB3 drives renal fibrosis through promoting histone lactylation-mediated NF- B activation [CUT&Tag]

Project description:Persistently elevated glycolysis in kidney has been demonstrated to promote chronic kidney disease. However, the underlying mechanism remains largely unclear. Here, we observed that PFKFB3, a key glycolytic enzyme, was remarkably induced in kidney proximal tubular cells following ischemia-reperfusion injury in mice, as well as in multiple etiologies of chronic kidney disease patients. Proximal tubular epithelial-specific deletion of PFKFB3 significantly reduced renal lactate levels, mitigated inflammation and fibrosis, and preserved renal function in the IRI mouse model. To explore the mechanism of PFKFB3 in renal fibrosis, we performed RNA-sequencing (RNA-seq) on the kidney cortices from IRI mice. Of note, we found that PFKFB3-mediated kidney tubular glycolytic reprogramming markedly enhanced H4K12la lactylation. To further explore the potential functional significance of H4K12la in renal fibrosis, we performed genome-wide cleavage under targets and tagmentation (CUT&Tag) analysis to identify candidate genes regulated by H4K12la in sham and IRI kidney. Following CUT&Tag, H4K12la-associated DNAs were amplified using non-biased conditions, labeled, and sequenced with Illumina NovaSeq 6000.

2024-05-01 | GSE266243 | GEO

PFKFB3 drives renal fibrosis through promoting histone lactylation-mediated NF- B activation [RNA-seq]

2024-05-01 | GSE266242 | GEO

Single-Nucleus RNA Sequencing Identifies New Classes of Proximal Tubular Epithelial Cells in Kidney Fibrosis

Project description:The study used a clinically relevant mouse model of chronic aristolochic acid nephropathy (AAN) to investigate the responses of proximal tubular cells during kidney fibrosis by single-nucleus RNA sequencing. The experiment involved 4 mice with AAN induced chronic renal fibrosis and 4 naive controls.

2021-06-23 | E-MTAB-9390 | biostudies-arrayexpress

WWP2 MEDIATES THE METABOLIC REPROGRAMMING OF RENAL MYOFIBROBLASTS TO PROMOTE KIDNEY FIBROSIS [ChIP-Seq]

Project description:Renal fibrosis is a common pathological endpoint that is challenging to reverse in chronic kidney disease (CKD) independently of the underlying causes. Although myofibroblasts are mainly responsible for the accumulation of a fibrillar collagen-rich extracellular matrix (ECM), recent reports revealed their heterogeneity in proliferative and fibrotic activities, mirroring specific metabolic states that drive fibrosis. Here, we investigate the role of E3 ubiquitin-protein ligase WWP2 in the metabolic reprogramming of renal myofibroblasts in fibrosis. The tubulointerstitial expression of WWP2 contributes to the progression of fibrosis in CKD patients and in pre-clinical models of CKD. WWP2 deficiency leads to increased fatty acid oxidation, boosting mitochondrial respiration, promoting myofibroblast proliferation and arresting pro-fibrotic activation, thus ameliorating kidney fibrosis. Specifically, WWP2 suppresses the transcription of PGC-1α, which mediates the metabolic and proliferative changes in fibrotic myofibroblasts. Pharmacological intervention targeting PGC-1α reverses the pro-fibrotic effect of WWP2. These findings reveal a previously unappreciated WWP2-PGC-1α axis underlying the metabolic reprogramming of myofibroblasts during renal fibrosis, which could provide a new target for therapeutic intervention in CKD.

2024-05-19 | GSE267765 | GEO

WWP2 MEDIATES THE METABOLIC REPROGRAMMING OF RENAL MYOFIBROBLASTS TO PROMOTE KIDNEY FIBROSIS [bulk RNA-seq]

2024-02-05 | GSE241503 | GEO

WWP2 MEDIATES THE METABOLIC REPROGRAMMING OF RENAL MYOFIBROBLASTS TO PROMOTE KIDNEY FIBROSIS [scRNA-seq]

2024-02-05 | GSE241502 | GEO