Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effect of CAR-M2 hydrogel treatment on the expression of related genes such as fibrosis and endothelial angiogenesis in mice with renal fibrosis (bulk RNA-seq)

ABSTRACT: Currently there is no effective treatment for renal fibrosis, which is the common outcome of chronic kidney disease (CKD). The renal fibrosis was aggravated by the unfavorable microenvironment and cell-to-cell interactions, accompanied by fibroblast activation and vascular rarefaction. Here, M2 macrophage engineered with chimeric antigen receptor (CAR) was created to promote renal revascularization for the synergistic treatment of phagocytosis of activated fibroblast. To achieve efficient delivery of parenchymal organs, a hydrogel was used to deliver CAR-M2 by renal subcapsule injection. CAR-M2 significantly reduced renal fibrosis and promoted revascularization. The single-cell RNA sequencing (scRNA-seq) revealed the heterogenicity and interaction of stroma and endothelial cells (ECs). A fibrosis-related Cxcr2+ EC subset was defined, which induced renal fibrosis by upregulating lipocalin 2 (Lcn2). Combined analysis of CKD patients demonstrated that CAR-M2 could release Matrix Metalloproteinase 2 (MMP2) in close proximity to activate the Cxcr2+ EC retinoid X receptor alpha (Rxra) to regulate fibrosis. Our study provides an effective strategy to develop an advanced cell therapy for organ fibrosis.

ORGANISM(S): Mus musculus

PROVIDER: GSE282078 | GEO | 2026/02/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Effect of CAR-M2 hydrogel treatment on the expression of related genes such as fibrosis and endothelial angiogenesis in mice with renal fibrosis

Project description:Kidney fibrosis involves the dynamic interactions of various cells, including immune cells, stromal cells, and ECs. Macrophages regulate regeneration and fibrosis through the interaction with other cell types, inducing some effects including the clearance of apoptotic myofibroblasts. Moreover, M2 macrophages promote tissue angiogenesis and participate in the reparative processes of soft tissue remodeling. Therefore, in addition to the direct effect of macrophage on renal fibrosis, its indirect regulatory role is also worthy to be explored. Its interaction with activated fibroblasts and ECs in renal fibrosis is unknown. Here our data discovered the heterogenicity and interaction of stroma and EC. Moreover, the infiltration of Cxcr2+ EC and expression of Lcn2 were indentfied highly related renal fibrosis. Taken together, our data provide a deeper understanding of the expression profile of renal fibrosis in mice, provide novel molecular targets for the treatment of renal fibrosis.

2026-02-06 | GSE252943 | GEO

Discovery of natural small-molecules to combat kidney fibrosis

Project description:Chronic kidney disease (CKD) has become one of the greatest threats to public health, characterized by renal fibrosis. However, no treatment targeting renal fibrosis is available so far. Several natural diterpene compounds exhibit extraordinary inhibitory effects on TGF-β1-induced renal fibroblast activation and renal fibrosis in UUO mouse model. RNA-sequencing reveals the signaling pathways affected by these compounds. The direct target of the compounds are explored via quantitative mass spectrometry. Besides, the efficacies of the compounds are compared with pirfenidone, an FDA-approved drug for idiopathic pulmonary fibrosis, which is under clinical trials for treating CKD patients. Moreover, these compounds exhibit more potent anti-fibrotic activities than conventional CKD medications such as valsartan and enalapril. Taken together, our study discovered that these diterpeniods alleviate kidney fibrosis by blocking the pro-fibrotic signaling pathway, which has great potential for the treatment of CKD.

2023-10-20 | GSE243694 | GEO

Genetic and pharmaceutical targeting of Suv39h1 ameliorates renal fibrosis by unlocking CXCL10 transcription [II]

Project description:Renal fibrosis is present in all forms of chronic kidney disease (CKD) and when dysregulated contributes to renal failure. Renal fibroblast is the major precursor to myofibroblast, the effector cell type of renal fibrosis. In the present study we investigated the role of Suv39h1, a lysine methyltransferase, in fibroblast-myofibroblast transition (FMyT) and renal fibrosis. We report that Su39h1 is up-regulated during FMyT both in vitro and in vivo. Suv39h1 deletion in fibroblasts partially blocked FMyT in vitro and attenuated renal fibrosis in three different animal models. Additionally, conditional Suv39h1 knockout in Postn+ mature myofibroblasts mitigated renal fibrosis in mice. Importantly, Suv39h1 inhibition with a small-molecule compound chaetocin suppressed FMyT in cell culture and ameliorated renal fibrosis in mice. Transcriptomic analysis uncovered CXCL10 as a downstream target for Suv39h1. CXCL10 knockdown nullified the protective effect of Suv39h1 insufficiency on renal fibrosis. Mechanistically, CXCL10 regulated FMyT by suppressing the Hippo/YAP pathway. In conclusion, our data illustrate a previously unrecognized role for Suv39h1 in regulating renal fibrosis.

2025-10-01 | GSE246192 | GEO

Genetic and pharmaceutical targeting of Suv39h1 ameliorates renal fibrosis by unlocking CXCL10 transcription [III]

2025-10-01 | GSE246190 | GEO

Genetic and pharmaceutical targeting of Suv39h1 ameliorates renal fibrosis by unlocking CXCL10 transcription [I]

2025-10-01 | GSE246089 | GEO

β-catenin-controlled tubular cell-derived exosomes play a key role in fibroblast activation via the OPN-CD44 axis

Project description:Tubular injury and peripheral fibroblast activation are the hallmarks of chronic kidney disease (CKD) and renal fibrosis, suggesting intimate communication between the two diseases. However, the underlying mechanisms remain to be determined. Exosomes play a role in shuttling proteins and other materials to recipient cells. In our study, we found that tubular cell-derived exosomes were aroused by β-catenin in kidney fibrogenesis. Osteopontin (OPN), especially its N-terminal fragments (N-OPN), was encapsulated in β-catenin-controlled tubular cell-derived exosome cargo, and subsequently passed to fibroblasts. Through binding with CD44, exosomal OPN promoted fibroblast proliferation and activation. Gene deletion of β-catenin in tubular cells (Ksp-β-catenin−/−) or gene ablation of CD44 (CD44−/−) greatly ameliorated renal fibrosis. Notably, N-OPN was secreted by exosome into the urine of patients with CKD, and negatively correlated with kidney function. The urinary exosomes from patients with CKD greatly accelerated renal fibrosis, which was blocked by CD44 deletion. These results suggest that exosome-mediated activation of the OPN/CD44 axis plays a key role in renal fibrosis, which is controlled by β-catenin.

2022-05-20 | PXD030696 | Pride

Tubular insulin-induced gene 1 deficiency promotes NAD+ consumption and exacerbates kidney fibrosis

Project description:<p>Profibrotic proximal tubular (PT) were identified as a unique phenotype of PTCs in renal fibrosis by single-cell RNA sequencing (scRNA-seq). Controlling the process of renal fibrosis requires understanding how to manage the S1 subset's branch to the S3 subset rather than to the profibrotic PT subset. Insulin-induced gene 1 (Insig1) is one of the branch-dependent genes involved in controlling this process, although its role in renal fibrosis is unknown. Here, we discovered that tubular Insig1 deficiency, rather than fibroblast Insig1 deficiency, play a detrimental role in the pathogenesis of renal fibrosis in vivo and in vitro. Overexpression of Insig1 profoundly inhibited renal fibrosis. Mechanistically, Insig1 deletion in PTCs boosted SREBP1 nuclear localization, increasing Aldh1a1 transcriptional activity, causing excessive NAD+ consumption and ER enlargement, as well as accelerating renal fibrosis. We also identified nicardipine as a selective inhibitor of Aldh1a1, which could restore NAD+ and maintain ER homeostasis, as well as improve renal fibrosis. Together, our findings support tubular Insig1 as a new therapeutic target for chronic kidney disease (CKD).</p>

2024-05-28 | MTBLS9985 | MetaboLights

Targeting FAM3D improves renal fibrosis via inhibiting tubular cell inflammation and pyroptosis

Project description:Renal fibrosis is the common pathological feature of CKD and plays a key role in the progression of CKD to ESRD. However, the underlying mechanisms of renal fibrosis initiation and progression remains unclear. FAM3D belongs to FAM3 gene family and is associate with nutrient regulation and inflammation. In this study, we found that FAM3D was de novo expressed in tubules during CKD and positively correlated with fibrogenesis. Knockout of tubular FAM3D effectively improved UIRI- or UUO-induced renal fibrosis. Mechanistically, FAM3D depletion suppressed NF-κB activation in epithelial cells via FPRs/MAPK pathway and then alleviated cell pyroptosis. Furthermore, blockade of FPR1/2 prevented renal inflammation, tubular cell pyroptosis, and fibrosis development. Our findings provided the first evidence for the critical role of FAM3D in renal fibrosis progression.

2025-10-01 | GSE243971 | GEO

Telomere dysfunction in renal epithelial cells leads to kidney fibrosis

Project description:Renal tubular epithelial cells (TECs) are critical mediators of renal fibrogenesis. Telomere dysfunction has been associated with renal injury and fibrosis. However, the role of telomere dysfunction specifically in TECs in the onset and progression of renal fibrosis remains poorly understood. To investigate the impact of telomere dysfunction on renal injury and fibrosis, we generated mice depleted for the shelterin component TRF1 specifically in TECs. Genetic ablation of Trf1 caused decline in renal function, tubular injury and tubulointerstitial fibrosis eight weeks after TRF1 depletion, concomitant with excessive accumulation of extracellular matrix (ECM), cell cycle arrest at G2/M phase, and telomeric damage. Trf1Δ/Δ mice activated regenerative repair mechanism, increasing the risk of of chronic kidney disease (CKD) progression following acute kidney injury (AKI), supporting proliferation-mediated telomere shortening in tubular cells. Mechanistically, Trf1 deletion upregulated Ras–Raf–Mek–Erk, PI3k/Akt/mTOR and p38 pathways. At humane endpoint, Trf1Δ/Δ mice displayed elevated urinary albumin-to-creatinine ratio (uACR), associated with augmented interstitial fibrosis and tubular atrophy eventually leading to CKD. In folic acid (FA)-induced nephropathy, depletion of Trf1 in TECs mitigated the fibrogenic phenotype of CKD. Collectively, our study underlies the important role of TECs in the development and progression of renal fibrosis and CKD associated to dysfunctional telomeres.

2025-08-21 | GSE272068 | GEO

Single-cell transcriptional profiling of advanced renal fibrosis identifies novel specific fibroblast marker and disease target

Project description:Dissecting the molecular and cellular nature of advanced renal fibrosis is principal for mechanistic understanding of chronic kidney disease (CKD) and developing targeted strategies against its progression. Aberrant renal fibroblast activation and unresolved tubular epithelial injury are key contributors to excessive extracellular matrix (ECM) production and kidney function loss. However, the transcriptional and cellular identities of activated renal fibroblasts remain poorly characterized. Moreover, historically used markers compromise specificity of activated renal fibroblasts tracing and targeting. Here, we created comprehensive single cell transcriptional profiles of two clinically relevant long-term renal fibrosis models and revealed three distinctive “secretory”, “contractile” and “migratory” fibroblast clusters. We identified a novel specific renal activated fibroblast marker expressed in all three populations. Advanced kidney fibrotic remodeling elicited sustaining developmental signature and pronounced epithelial-to-stromal crosstalk. Furthermore, we mechanistically validated AHNAK as a putative novel target of kidney injury in a primary human in vitro model of epithelial-to-mesenchymal transition.

2023-06-14 | GSE198621 | GEO