{"database":"ENA","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Fastqsanger.gz":["ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/002/SRR34089802/SRR34089802_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/003/SRR34089803/SRR34089803_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/004/SRR34089804/SRR34089804_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/097/SRR34089797/SRR34089797_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/099/SRR34089799/SRR34089799_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/098/SRR34089798/SRR34089798_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/003/SRR34089803/SRR34089803_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/002/SRR34089802/SRR34089802_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/099/SRR34089799/SRR34089799_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/096/SRR34089796/SRR34089796_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/000/SRR34089800/SRR34089800_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/001/SRR34089801/SRR34089801_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/000/SRR34089800/SRR34089800_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/096/SRR34089796/SRR34089796_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/001/SRR34089801/SRR34089801_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/098/SRR34089798/SRR34089798_2.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/097/SRR34089797/SRR34089797_1.fastq.gz","ftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR340/004/SRR34089804/SRR34089804_1.fastq.gz"]},"type":"primary"},"statusCodeValue":200,"statusCode":"OK"}],"scores":null,"additional":{"omics_type":["Genomics"],"center_name":["Fornoni, University of Miami"],"full_dataset_link":["https://www.ebi.ac.uk/ena/browser/view/PRJNA1279954"],"scientific_name":["Mus musculus"],"long_description":["Background: Renal lipid dysmetabolism contributes to glomerular disease progression, including Alport Syndrome. We recently identified alterations in the apolipoprotein M/sphingosine-1-phosphate/sphingosine-1-phosphate receptor 4 signaling axis in glomeruli from patients with glomerular disease. Methods: We utilized Col4a3 knockout mice and immortalized podocytes derived from these mice as a mouse model of Alport Syndrome. Mice and podocytes were treated with recombinant apolipoprotein M or the sphingosine-1-phosphate receptor 4 antagonist, CYM50358. Results: Col4a3-/- glomeruli and podocytes exhibited reduced apolipoprotein M and increased sphingosine-1-phosphate receptor 4 expression and increased sphignsoine-1-phosphate levels, mirroring findings in patients with glomerular disease. Treatment with apolipoprotein M or CYM50358 reduced albuminuria, BUN, and plasma creatinine, and ameliorated glomerulosclerosis, tubulointerstitial fibrosis, podocyte loss and foot process effacement. Both treatments reduced triglyceride and cholesterol accumulation in glomeruli and podocytes. RNA-seq analysis of Col4a3-/- revealed that sphingosine-1-phosphate receptor 4 antagonism upregulated lysosomal and autophagy-related genes. Western blot analysis confirmed increased LC3-II/LC3-I ratios and decreased p62, indicating enhanced autophagic flux. Treated podocytes showed increased lysosome numbers and co-localization with lipid droplets. In contrast, apolipoprotein M had no effect on autophagy but promoted cholesterol efflux. Conclusions: The apolipoprotein M/sphingosine-1-phosphate axis is dysregulated in Col4a3-/- podocytes. Targeting this pathway through apolipoprotein M supplementation or sphingosine-1-phosphate receptor 4 antagonism improves renal function and reduces lipid accumulation by enhancing either cholesterol efflux or autophagy, respectively. These findings suggest that restoring lipid homeostasis via targeting the APOM/S1P/S1PR4 axis may be a promising therapeutic strategy for Alport Syndrome and other glomerular diseases. Overall design: We treated Col4a3-/- podocytes with either a s1pr4 antagonist (CYM50358) or treated them with exogenous apolipoprotein M for 24 hours and extracted RNA"],"repository":["ENA"],"additional_accession":[]},"is_claimable":false,"name":"Inhibition of S1PR4 and supplementation of APOM in Alport Podocytes","description":"Inhibition of S1PR4 and supplementation of APOM in Alport Podocytes","dates":{"last_updated":"2025-09-24","first_public":"2025-06-29"},"accession":"PRJNA1279954","cross_references":{"GEO":["GSE300237"],"taxon":["10090"]}}