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| Status |
Public on Dec 01, 2024 |
| Title |
Glucocorticoid- and Pioglitazone-Induced Proteinuria Reduction in Experimental Nephrotic Syndrome Both Correlate with Glomerular ECM Modulation |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Idiopathic nephrotic Syndrome (NS) is a common glomerular disease. While glucocorticoids (GC) are the primary treatment, the PPARĪ³ agonist pioglitazone (Pio) also reduces proteinuria in patients with NS and directly protects podocytes from injury. Since both drugs reduce proteinuria, we hypothesized these effects result from overlapping transcriptional patterns. Systems biology approaches compared glomerular transcriptomes from rats with PAN-induced NS treated with GC vs. Pio and identified 29 commonly regulated genes-of-interest, primarily involved in extracellular matrix (ECM) remodeling. Correlation with clinical idiopathic NS patient datasets confirmed glomerular ECM dysregulation as a potential mechanism of injury. Cellular deconvolution in silico revealed GC- and Pio-induced amelioration of altered genes primarily within podocytes and mesangial cells. While validation studies are indicated, these analyses identified molecular pathways involved in the early stages of NS (prior to scarring) suggesting that targeting glomerular ECM dysregulation may enable a future non-immunosuppressive approach for proteinuria reduction in idiopathic NS.
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| Overall design |
Day 11 glomeruli were isolated from rats with PAN-induced NS treated with methylprednisolone or with pioglitazone. Sham treated health controls were included as reference. N=4 rats were used for RNAseq. Data were analyzed for PAN-induced changes in gene expression and amelioration of said alterations by either drug. This study focused on the overlapping amerliorations of disease-induced gene expression between methylprednisolone and pioglitazone.
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| Contributor(s) |
Bhayan S, Dougherty JA, Kamigaki Y, Agrawal S, Wijeratne S, Fitch J, Waller AP, Wolfgang KJ, White P, Kerlin BA, Smoyer WE |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Nov 16, 2023 |
| Last update date |
Dec 02, 2024 |
| Contact name |
William E Smoyer |
| E-mail(s) |
[email protected]
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| Organization name |
Nationwide Children's Hospital, Columbus, Ohio
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| Department |
Research
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| Lab |
Smoyer
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| Street address |
700 Children's Dr, Research Building 2
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| City |
Columbus |
| State/province |
OH |
| ZIP/Postal code |
43205 |
| Country |
USA |
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| Platforms (1) |
| GPL22396 |
Illumina HiSeq 4000 (Rattus norvegicus) |
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| Samples (16)
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| GSM7905282 |
Sham Control, rep4 |
| GSM7905283 |
PAN only, rep1 |
| GSM7905284 |
PAN only, rep2 |
| GSM7905285 |
PAN only, rep3 |
| GSM7905286 |
PAN only, rep4 |
| GSM7905287 |
PAN + MP, rep1 |
| GSM7905288 |
PAN + MP, rep2 |
| GSM7905289 |
PAN + MP, rep3 |
| GSM7905290 |
PAN + MP, rep4 |
| GSM7905291 |
PAN + Pio, rep1 |
| GSM7905292 |
PAN + Pio, rep2 |
| GSM7905293 |
PAN + Pio, rep3 |
| GSM7905294 |
PAN + Pio, rep4 |
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| Relations |
| BioProject |
PRJNA1041459 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE248053_AllData_160322_RNASeq_Smoyer_Results_iScience.xlsx |
11.3 Mb |
(ftp)(http) |
XLSX |
| GSE248053_RAW.tar |
2.1 Mb |
(http)(custom) |
TAR (of COV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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