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Podocyte-specific induction of Krüppel-like factor 15 restores differentiation markers and attenuates kidney injury in proteinuric kidney disease

ABSTRACT: Podocyte-specific induction of Krüppel-like factor 15 restores differentiation markers and attenuates kidney injury in proteinuric kidney disease

PROVIDER: PRJNA483939 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR7632730.fastq.gz	Fastqsanger.gz
	SRR7632731.fastq.gz	Fastqsanger.gz
	SRR7632722.fastq.gz	Fastqsanger.gz
	SRR7632732.fastq.gz	Fastqsanger.gz
	SRR7632723.fastq.gz	Fastqsanger.gz

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Similar Datasets

Podocyte-specific induction of Krüppel-like factor 15 restores differentiation markers and attenuates kidney injury in proteinuric kidney disease

Project description:Podocyte injury is the hallmark of proteinuric kidney diseases, such as Focal Segmental Glomerulosclerosis and Minimal Change Disease. Therapeutic strategies in the management of proteinuric diseases are limited. Although agents such as glucocorticoids, cyclosporine, and rituximab have direct effects on the podocyte by stabilizing its actin cytoskeleton, these drugs are riddled with systemic toxicity and off-target effects that hinder their chronic use. We previously demonstrated that the loss of the kidney-enriched zinc finger transcription factor, Krüppel-like factor 15 (KLF15), increases susceptibility to proteinuric kidney disease as well as attenuates the salutary effects of retinoic acid and glucocorticoids in the podocyte. Here, we show that podocyte-specific induction of KLF15, using the tetracycline-inducible system, attenuated podocyte injury, glomerulosclerosis, tubulointerstitial fibrosis and inflammation, while improving renal function and overall survival in HIV-1 transgenic mice. Enrichment analysis of mRNA sequencing of isolated glomerular extracts from this model shows that podocyte-specific induction of KLF15 activates pathways involved in stabilization of actin cytoskeleton, focal adhesion, and podocyte differentiation. Transcription factor enrichment analysis, with further experimental validation, suggests that KLF15 activity is in part mediated by Wilms Tumor 1 (WT1), a transcription factor known to be critical for podocyte differentiation. Further, we confirmed the benefits of podocyte-specific induction of KLF15 in the adriamycin-induced proteinuric murine model. Collectively, these observations suggest that induction of KLF15 might be a potential therapeutic target in the treatment of proteinuric kidney disease.

2018-08-02 | GSE117987 | GEO

A kidney specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

Project description:A kidney specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

| PRJNA1004582 | ENA

A kidney specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

Project description:A kidney specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

| PRJNA1016413 | ENA

A kidney specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

2025-07-30 | GSE243131 | GEO

A kidney specific fasting-mimicking diet induces podocyte reprogramming and restores renal function in glomerulopathy

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

Podocyte-Specific Induction of Kruppel-Like Factor 15 Restores Differentiation Markers and Attenuates Kidney Injury in Proteinuric Kidney Disease.

Project description:BACKGROUND:Podocyte injury is the hallmark of proteinuric kidney diseases, such as FSGS and minimal change disease, and destabilization of the podocyte's actin cytoskeleton contributes to podocyte dysfunction in many of these conditions. Although agents, such as glucocorticoids and cyclosporin, stabilize the actin cytoskeleton, systemic toxicity hinders chronic use. We previously showed that loss of the kidney-enriched zinc finger transcription factor Krüppel-like factor 15 (KLF15) increases susceptibility to proteinuric kidney disease and attenuates the salutary effects of retinoic acid and glucocorticoids in the podocyte. METHODS:We induced podocyte-specific KLF15 in two proteinuric murine models, HIV-1 transgenic (Tg26) mice and adriamycin (ADR)-induced nephropathy, and used RNA sequencing of isolated glomeruli and subsequent enrichment analysis to investigate pathways mediated by podocyte-specific KLF15 in Tg26 mice. We also explored in cultured human podocytes the potential mediating role of Wilms Tumor 1 (WT1), a transcription factor critical for podocyte differentiation. RESULTS:In Tg26 mice, inducing podocyte-specific KLF15 attenuated podocyte injury, glomerulosclerosis, tubulointerstitial fibrosis, and inflammation, while improving renal function and overall survival; it also attenuated podocyte injury in ADR-treated mice. Enrichment analysis of RNA sequencing from the Tg26 mouse model shows that KLF15 induction activates pathways involved in stabilization of actin cytoskeleton, focal adhesion, and podocyte differentiation. Transcription factor enrichment analysis, with further experimental validation, suggests that KLF15 activity is in part mediated by WT1. CONCLUSIONS:Inducing podocyte-specific KLF15 attenuates kidney injury by directly and indirectly upregulating genes critical for podocyte differentiation, suggesting that KLF15 induction might be a potential strategy for treating proteinuric kidney disease.

| S-EPMC6171275 | biostudies-literature

Transcriptomic analysis of kidney cortex following podocyte-loss of Klf4

Project description:The goal of this study was to identify transcriptomic changes of mouse kidney cortex in mice with podocyte-specific deletion of Kruppel-like factor 4, a zinc-finger transcription factor.

2021-09-22 | GSE149818 | GEO

Single cell transcriptomics reveal disrupted kidney filter cell-cell interactions after early and selective podocyte injury

Project description:We recently demonstrated that podocyte ablation via doxycycline-inducible deletion of an essential endogenous molecule, CTCF (iCTCFpod-/-), is sufficient to drive progressive CKD. However, the earliest events connecting podocyte injury to disrupted intercellular communication within the kidney filter remain unclear. Here we performed single-cell RNA sequencing of kidney tissue from iCTCFpod-/- mice after one week of doxycycline induction to generate a map of the earliest transcriptional effects of podocyte injury on cell-cell interactions at single cell resolution

2021-05-09 | GSE174102 | GEO

Glomerular podocyte RNA-seq data of the podocyte-specific Profilin1 deficient mice

Project description:The progression of proteinuric kidney disease is associated with podocyte loss but the mechanisms remain unclear. Podocytes reenter the cell cycle to repair damaged ds DNA breaks. However, unsuccessful repair results in podocytes crossing the G1/S checkpoint and undergoes abortive cytokinesis. In this study, we identified Pfn1 as a major contributor in maintaining glomerular integrity and its loss in mice results in severe proteinuria, and kidney failure due to podocyte mitotic catastrophe, characterized by abundant multinucleated cells. Reentry of podocytes were identified by using FUCCI-2aR mice, accompanying the alteration of cell-cycle associated proteins, such as P21, P53, Cyclin B, and Cyclin D. Podocyte-specific translating ribosome affinity purification (TRAP) and RNAseq revealed a reduction of Ribosomal RNA-processing protein 8 (Rrp8) and re-expression of Rrp8 partially rescued the in-vitro phenotype. Clinical analysis of patients with proteinuric kidney disease demonstrated multinucleated podocytes and reduced podocyte profilin1 in kidney tissue. These results suggest that profilin is indispensible in regulating podocyte cell cycle and its disruption contributes to podocyte loss through mitotic catastrophe.

2023-12-01 | GSE227414 | GEO

Gene expression profile at single cell level of podocyte-specific I-PpoI expressing mice kidney cortex

Project description:To investigate the alterations in cell populations in the kidney after podocyte DNA DSBs, we performed single-cell RNA sequencing (scRNA-seq) on the renal cortex of 12-week-old podocyte-specific I-PpoI expressing mice that had not yet developed glomerulosclerosis or fibrosis.

2022-12-26 | GSE220478 | GEO

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