M2-like macrophages in the injured-kidney cortex promoted kidney cancer progression via the direct pro-tumor effect and the inhibition of CD8 T cell infiltration
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PROVIDER: PRJNA810701 | ENA |
REPOSITORIES: ENA
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Project description:In this study, we aimed to evaluate the effect of M2-like macrophages in the injured kidney on kidney cancer progression. As an acute kidney injury to chronic kidney disease model, we used unilateral ischemia-reperfusion injury (uIRI). And we inoculated RenCa cells, which are murine kidney cancer cell line, into renal subcapsule 14 days after uIRI (uIRI-Can) and compared uIRI-Can to RenCa cells inoculated into sham-operated renal subcapsule (Sham-Can) 20 days after inoculation. To identify gene characteristics of M2-like macrophages that are commonly detected both in the uIRI kidney cortex and uIRI-Can, we sorted Ly6Clow macrophages from 4 groups, uIRI kidney cortex, sham kidney cortex, uIRI-Can, and Sham-Can, and conducted RNA-Seq. This study revealed the characteristic gene expression of M2-like macrophages which were commonly detected in the injured kidney cortex and kidney cancer progressed on the injured kidney. And this could be a future therapeutic target of macrophage-targeted therapy.
2022-12-06 | GSE197494 | GEO
Project description:Renal recovery following injury relies on cellular regeneration. In the mouse kidney following injury, injured epithelial cells undergoes de-differentiate, proliferate and re-differentiate into functional cells, following a a tightly controlled genetic programme where specific sets of genes are up-regulated. We used microarrays to detail the global programme of gene expression underlying cellular regeneration following injury with or without a HDAC inhibitor, m4PTB, treatment and identified distinct classes of up-regulated genes during this process.
2013-03-01 | GSE42247 | GEO
Project description:Excessive renal fibrosis is a common pathology in progressive chronic kidney diseases. Inflammatory injury and aberrant repair processes contribute to the development of kidney fibrosis. Myeloid cells, particularly monocytes/macrophages, play a crucial role in kidney fibrosis by releasing their proinflammatory cytokines and extracellular matrix components such as collagen and fibronectin into the microenvironment of the injured kidney. Numerous signaling pathways have been identified in relation to these activities. However, the involvement of metabolic pathways in myeloid cell functions during the development of renal fibrosis remains understudied. In our study, we initially reanalyzed single-cell RNA sequencing data of renal myeloid cells from Dr. Denby’s group and observed an increased glycolytic pathway in myeloid cells that are critical for renal inflammation and fibrosis. To investigate the role of myeloid glycolysis in renal fibrosis, we utilized a model of unilateral ureteral obstruction in mice deficient of Pfkfb3, an activator of glycolysis, in myeloid cells (Pfkfb3ΔMϕ) and their wild type littermates (Pfkfb3WT). We observed a significant reduction in fibrosis in the obstructive kidneys of Pfkfb3ΔMϕ mice compared to Pfkfb3WT mice. This was accompanied by a substantial decrease in myeloid cell infiltration, as well as a decrease in the numbers of M1 and M2 macrophages and suppression of macrophage to obtain myofibroblast phenotype in the obstructive kidneys of Pfkfb3ΔMϕ mice. Mechanistic studies indicate that glycolytic metabolites stabilize HIF1α, leading to alterations in macrophage phenotypes that contribute to renal fibrosis. In conclusion, our study implicates that targeting myeloid glycolysis represents a novel approach to inhibit renal fibrosis.
2024-03-12 | MTBLS8278 | MetaboLights
Project description:Injured kidney organoids gene expression profile at single cell
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Project description:RNA-seq results of the kidney of male kidney-specific G9a knockout mice after acute kidney injured
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Project description:Aging involves morphological and functional changes across different organs, but how these changes are linked among the different organs remains to be elucidated. Here, we uncover a central role of platelets in sys temic aging. In aged mice, the levels of platelet secreted pro inflammatory factors (PSPF) increased greatly in the serum and platelets, leading to a diffuse increase of platelet infiltration in brain, liver, lung, kidney, and aortic root. The RNA binding protein HuR/ELAVL1, a major regulator of R NA metabolism, promoted the production of PSPF in platelets. Platelet specific deletion of HuR reduced the expression of PSPF in platelets, alleviated platelet infiltration in brain, liver, lung, kidney, and aortic root, and delayed systemic aging. Our findings highlight a role of platelets in coordinating aging traits across organs.
2024-11-16 | GSE281572 | GEO
Project description:Renal recovery following injury relies on cellular regeneration. In the mouse kidney following injury, injured epithelial cells undergoes de-differentiate, proliferate and re-differentiate into functional cells, following a a tightly controlled genetic programme where specific sets of genes are up-regulated. We used microarrays to detail the global programme of gene expression underlying cellular regeneration following injury with or without a HDAC inhibitor, m4PTB, treatment and identified distinct classes of up-regulated genes during this process. Male BALB/c mice underwent 26 minute unilateral ischemia-reperfusion (IR) with contralateral nephrectomy treated with vehicle or 100 mg/kg m4PTB 24 h after inducing renal injury, and kidneys harvested for RNA extraction 12 h later. We sought to obtain kidneys within a similar degree of injury in order to carefully evaluate the effect of m4PTB on expression profiles. To that end, we selected kidneys according to three different criteria of injury: (1) level of serum creatinine at Day1, (2) the level of blood urea nitrogen (BUN) (3) Kim1 expression by qPCR at Day1.5 using haevested kidneys
2013-03-01 | E-GEOD-42247 | biostudies-arrayexpress
Project description:Background: Tumor-associated macrophages (TAMs) are an important component of the tumor microenvironment (TME). However, the crosstalk between esophageal squamous cell carcinoma (ESCC) cells and TAMs remains largely unexplored. Methods: Clinical samples and the TCGA database were used to evaluate the relevance of SPP1 and TAM infiltration in ESCC. Mouse models were constructed to investigate the roles of macrophages educated by SPP1 in ESCC. Macrophage phenotypes were determined using qRT‒PCR and immunohistochemical staining. RNA sequencing was performed to elucidate the mechanism. Results: Increasing expression of SPP1 correlated with M2-like TAM accumulation in ESCC, and they both predicted poor prognosis in the ESCC cohort. Knockdown of SPP1 significantly inhibited the infiltration of M2 TAMs in xenograft tumors. In vivo mouse model experiments showed that SPP1-mediated education of macrophages plays essential roles in the progression of ESCC. Mechanistically, SPP1 recruited macrophages and promoted M2 polarization via CD44/PI3K/AKT signaling activation and then induced VEGFA and IL6 secretion to sustain ESCC progression. Finally, blockade of SPP1 with RNA aptamer significantly inhibited tumor growth and M2 TAM infiltration in xenograft mouse models. Conclusions: This study highlights a SPP1-mediated crosstalk between ESCC cells and TAMs in ESCC. SPP1 could serve as a potential target in ESCC therapy.
2024-09-09 | GSE256360 | GEO
Project description:Hyperuricemia is an essential risk factor in chronic kidney disease (CKD), while urate-lowering therapy to prevent or delay CKD is controversial. Alternatively activated macrophages in response to local microenvironment play diverse roles in kidney diseases. Here, we aim to investigate whether and how macrophage integrin αM (ITGAM) contributes to hyperuricemia-related CKD. In vivo, we explored dynamic characteristics of renal tissue in C57BL/6J mice with hyperuricemia-related CKD. By incorporating transcriptomics and phosphoproteomics data, we analyzed gene expression profile, hub genes and potential pathways. In vitro, we validated bioinformatic findings under different conditions with interventions corresponding to core nodes. We found that hyperuricemia-related CKD was characterized by elevated serum uric acid levels, impaired renal function, activation of macrophage alternative (M2) polarization, and kidney fibrosis. Integrated bioinformatic analyses revealed Itgam as the potential core gene and was associated with focal adhesion signaling. Notably, we confirmed the upregulated expression of macrophage ITGAM, activated pathway, and macrophage M2 polarization in injured kidneys. In vitro, through silencing Itgam, inhibiting p-FAK or p-AKT1 phosphorylation, and concurrent inhibiting of p-FAK while activating p-AKT1 all contributed to the modulation of macrophage M2 polarization. Our results indicated targeting macrophage ITGAM might be a promising therapeutic approach for preventing CKD.
2024-06-26 | GSE262687 | GEO