The Use of High-Throughput Transcriptomics to Identify Pathways with Therapeutic Significance in Podocytes.
Ashish Kumar SolankiPankaj SrivastavaBushra RahmanJoshua H LipschutzDeepak NihalaniEhtesham ArifPublished in: International journal of molecular sciences (2019)
Podocytes have a unique structure that supports glomerular filtration function, and many glomerular diseases result in loss of this structure, leading to podocyte dysfunction and ESRD (end stage renal disease). These structural and functional changes involve a complex set of molecular and cellular mechanisms that remain poorly understood. To understand the molecular signature of podocyte injury, we performed transcriptome analysis of cultured human podocytes injured either with PAN (puromycin aminonucleoside) or doxorubicin/adriamycin (ADR). The pathway analysis through DE (differential expression) and gene-enrichment analysis of the injured podocytes showed Tumor protein p53 (P53) as one of the major signaling pathways that was significantly upregulated upon podocyte injury. Accordingly, P53 expression was also up-regulated in the glomeruli of nephrotoxic serum (NTS) and ADR-injured mice. To further confirm these observations, cultured podocytes were treated with the P53 inhibitor pifithrin-α, which showed significant protection from ADR-induced actin cytoskeleton damage. In conclusion, signaling pathways that are involved in podocyte pathogenesis and can be therapeutically targeted were identified by high-throughput transcriptomic analysis of injured podocytes.
Keyphrases
- high glucose
- endothelial cells
- high throughput
- single cell
- end stage renal disease
- diabetic nephropathy
- chronic kidney disease
- peritoneal dialysis
- signaling pathway
- adverse drug
- rna seq
- poor prognosis
- oxidative stress
- genome wide
- gene expression
- cancer therapy
- drug delivery
- pi k akt
- type diabetes
- amino acid
- copy number
- transcription factor
- adipose tissue
- metabolic syndrome
- electronic health record
- induced apoptosis