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Streptozotocin induces renal proximal tubular injury through p53 signaling activation

ABSTRACT: Streptozotocin induces renal proximal tubular injury through p53 signaling activation

PROVIDER: PRJNA889805 | ENA |

REPOSITORIES: ENA

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Streptozotocin induces renal proximal tubular injury through p53 signaling activation

Project description:Streptozotocin (STZ) is an anti-cancer drug that is primarily used to treat neuroendocrine tumors (NETs) in clinical settings and develop type 1 diabetes rodent models in experimental fields. STZ is incorporated into cells through the glucose transporter, GLUT2, which is primarily expressed in pancreatic β-cells or proximal tubular epithelial cells in the kidney. However, its cytotoxic effects on kidney cells have been underestimated and the underlying mechanisms remain unclear. We herein demonstrated that DNA damage and subsequent p53 signaling were responsible for the development of STZ-induced tubular epithelial injury. We detected tubular epithelial DNA damage in NET patients treated with STZ. Unbiased transcriptomics of tubular epithelial cells in vitro showed the activation of the p53 signaling pathway by STZ. STZ induced DNA damage and activated p53 signaling in vivo in a dose-dependent manner, resulting in reduced membrane transport. The localization of STZ-induced kidney injury was limited to within the kidney cortex, which was independent of blood glucose. The pharmacological inhibition of p53 and sodium-glucose transporter 2 (SGLT2) mitigated STZ-induced epithelial injury. However, the cytotoxic effects of STZ on pancreatic β-cells were preserved in SGLT2 inhibitor-treated mice. The present results demonstrate the strong proximal tubular-specific cytotoxicity of STZ and the underlying mechanisms in vivo, which may be ameliorated by a SGLT2 inhibitor pretreatment. Since the cytotoxic effects of STZ against β-cells were not impaired by dapagliflozin, a pretreatment with a SGLT2 inhibitor has potential as a preventative remedy for kidney injury in NET patients treated with STZ.

2023-06-07 | GSE215337 | GEO

Expression data from Stx2-treated human renal proximal tubular epithelial cell (RPTEC)

Project description:Shiga toxin type 2 (Stx2) from Escherichia coli is thought to be a main factor to casue renal dysfunction in Enterohemorrhagic E. coli (EHEC) infection. The renal dysfunction caused by the proximal tubular defects can be detected in the earlier EHEC infection. However, the precise information of gene expression from proximal tubular epithelial cells has yet to be clarified. We performed microarray experiments using Stx2-injected mouse kidney and Stx2-treated human renal proximal tubular epithelial cells (RPTEC), and extracted common genes that were differentially expressed.

2022-01-01 | GSE172466 | GEO

Canagliflozin impact on human renal proximal tubular cells (HK2)

Project description:The impact of canagliflozin on gene expression changes was investigated in human renal proximal tubular cells (HK2) after pre-treatment with high glucose.

2019-02-27 | GSE106156 | GEO

Transcription profiling by array of human renal proximal tubular cell cultures treated with nephrotoxins

Project description:This experiment is designed to investigate common transcriptional alterations in renal proximal tubular cell cultures due to nephrotoxin exposure.

2011-02-01 | E-MEXP-2599 | biostudies-arrayexpress

Canagliflozin impact on human renal proximal tubular cells (HK2)

Project description:Canagliflozin impact on human renal proximal tubular cells (HK2)

| PRJNA415785 | ENA

Transcription profiling of human renal proximal tubular cell line HK-2 treated with Cyclosporine A timecourse 0, 12, 48 hours

Project description:Effect of 4.2 micromolar Cyclosporine A on human renal proximal tubular cell line HK-2 over 48 hours

2008-06-11 | E-GEOD-1403 | biostudies-arrayexpress

Cloning and variation of adult renal tubular progenitors

Project description:Kidney damage involves the progressive and inexorable destruction of tubular and glomerular system. However, it is known that the patients survive AKI often recover renal structure and function. Correspondingly, previous studies demonstrated tubular regeneration in mice after massive kidney injury and linked mouse Sox9+ renal progenitor cells to this process. Here we show that renal progenitor cells can be cloned from renal needle biopsy sample of CKD patients. Progenitor cells can readily assembly into “kidney organoids” expressing proximal/distal tubular cell markers in 3D culture.

2022-04-22 | GSE119426 | GEO

Analysis of altered microRNA expression profiles in proximal renal tubular cells in response to calcium oxalate monohydrate crystal adhesion

Project description:The present study aims to assess the potential changes in microRNAs of proximal renal tubular cells in response to the adhesion of calcium oxalate monohydrate (COM) crystals.

2014-04-22 | GSE56934 | GEO

Expression data from proximal tubular cells of proximal tubular cell-specific KAT5 knockout mice

Project description:Isolated proximal tubular cells from proximal tubular cell-specific KAT5 knockout mice for RNA extraction and hybridization on Affymetrix microarrays. We sought to obtain the physiological significance of KAT5 in proximal tubular cells.

2021-11-19 | GSE168535 | GEO

Analysis of altered microRNA expression profiles in proximal renal tubular cells in response to calcium oxalate monohydrate crystal adhesion

Project description:The present study aims to assess the potential changes in microRNAs of proximal renal tubular cells in response to the adhesion of calcium oxalate monohydrate (COM) crystals. microRNA microarray was applied to evaluate the expression of HK-2 cells exposed to COM crystals for 0 and 24 hours.

2014-04-22 | E-GEOD-56934 | biostudies-arrayexpress

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