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PA up-regulates the KEGG pathway ‘Lysosome’ in cultured PTECs

ABSTRACT: PA up-regulates the KEGG pathway ‘Lysosome’ in cultured PTECs

PROVIDER: PRJNA790618 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17272445_1.fastq.gz	Fastqsanger.gz
	SRR17272445_2.fastq.gz	Fastqsanger.gz
	SRR17272446_1.fastq.gz	Fastqsanger.gz
	SRR17272446_2.fastq.gz	Fastqsanger.gz
	SRR17272447_1.fastq.gz	Fastqsanger.gz

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PA up-regulates the KEGG pathway ‘Lysosome’ in cultured PTECs

Project description:Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in experimental and human obesity-related kidney disease. However, the transcriptional regulators involved in renal lipotoxicity is largely unknown. Here we found palmitic acid (PA) strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB), which was mediated by inhibition of MTORC1 (mechanistic target of rapamycin kinase complex 1) via Rag GTPase inactivation. PA-induced TFEB nuclear translocation was, however, gradually decreased over a longer treatment. We then investigated the role of TFEB in the pathogenesis of obesity-related kidney disease. High-fat diet (HFD)-fed proximal tubular epithelial cell (PTEC)-specific Tfeb-deficient mice exhibited greater phospholipid accumulation in enlarged lysosomes, which manifested as multilamellar bodies (MLBs). Activated TFEB mediated lysosomal exocytosis of phospholipids, to help PTECs to reduce MLBs/vacuole accumulation. Furthermore, HFD-fed PTEC-specific Tfeb-deficient mice showed autophagic stagnation and exacerbated injury upon renal ischemia-reperfusion. Finally, higher BMI was associated with increased vacuolation and decreased nuclear TFEB in the proximal tubule of CKD patients and we herein proposed a new disease concept “obesity-related tubulopathy (ORT)”. In conclusion, these results indicate a critical role of TFEB-mediated lysosomal exocytosis in counteracting renal lipotoxicity.

2023-01-17 | GSE191216 | GEO

RNA-seq of AML12 cells treated with PA+si-NC/PA+si-circ-SLC9A6

Project description:We analyzed the global RNA expression profile in circ-SLC9A6-deficient AML12 cells under PA stimulation，and found that 84 mRNAs are up-regulated and 307 are down-regulated.

2024-09-05 | GSE237554 | GEO

Acidiphilium sp. PA strain:PA

Project description:Acidiphilium sp. PA strain:PA Genome sequencing and assembly

| PRJNA756838 | ENA

Gene expression changes in rat liver induced by 6 PA

Project description:Pyrrolizidine alkaloids (PA) are secondary plant metabolites that occur as food and feed contaminants. Acute and subacute PA poisoning can lead to severe liver damage in humans and animals. Chronic exposure to low levels of PA can induce liver cirrhosis and liver cancer. However, it is not well understood which transcriptional changes are induced by PA and whether all hepatotoxic PA, regardless of their structure, induce similar responses. Therefore, a 28-day subacute rat feeding study was performed with six structurally different PA heliotrine, echimidine, lasiocarpine, senecionine, senkirkine, and platyphylline, administered at not acutely toxic doses from 0.1 to 3.3 mg/kg body weight. This dose range is relevant for humans, since consumption of contaminated tea may result in doses of ~8 µg/kg in adults and cases of PA ingestion by contaminated food was reported for infants with doses up to 3 mg/kg. ALT and AST were not increased in all treatment groups. Whole genome microarray analyses revealed pronounced effects on gene expression in the high-dose treatment groups resulting in a set of 36 commonly regulated genes. However, platyphylline, the only 1,2-saturated and therefore presumably non-hepatotoxic PA, did not induce significant expression changes. Biological functions identified to be affected by high dose treatments (3.3 mg/kg body weight) comprise cell cycle regulation associated with DNA damage response. These functions were found to be affected by all analyzed 1,2-unsaturated PA. Transcriptomic analysis with six structurally different PA heliotrine, echimidine, lasiocarpine, senecionine, senkirkine, and platyphylline after subacute treatment of rats

2020-05-01 | GSE149678 | GEO

GEMARA-XDR-PA

Project description:GEMARA-XDR-PA

| PRJEB31047 | ENA

Staphylococcus aureus PA strain:PA

Project description:Staphylococcus aureus PA Genome sequencing project

| PRJNA68117 | ENA

Pseudomonas aeruginosa strain:PA-1 | isolate:PA-1

Project description:Pseudomonas aeruginosa strain:PA-1 | isolate:PA-1 Genome sequencing

| PRJNA839740 | ENA

Pseudomonas aeruginosa strain:PA-2 | isolate:PA-2

Project description:Pseudomonas aeruginosa strain:PA-2 | isolate:PA-2 Genome sequencing