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Published on: March 4, 2022
Proteomics reveals the key transcription-related factors mediating obstructive nephropathy in pediatric patients and
Hualin Cao1, Yuandong Tao2,3, Ruyue Jin2,3
1Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Insights
This study identifies key transcription-related factors (TRFs) involved in pediatric obstructive nephropathy. It reveals dysregulated TRFs in inflammation and fibrosis pathways, offering new molecular insights into kidney injury.
Area of Science:
- Pediatric Nephrology
- Molecular Biology
- Genomics
Background:
- Obstructive nephropathy is a primary cause of kidney injury in children.
- Transcription-related factors (TRFs) are increasingly linked to kidney diseases.
- A comprehensive analysis of TRFs in pediatric obstructive nephropathy is lacking.
Purpose of the Study:
- To identify and characterize the global landscape of dysregulated TRFs in pediatric obstructive nephropathy.
- To explore the molecular mechanisms underlying kidney injury in this condition.
Main Methods:
- Proteomic data from pediatric patients and unilateral ureteral obstruction (UUO) mouse models were analyzed.
- Gene Ontology (GO) analysis identified enriched pathways.
- Immunoblotting verified key TRFs in patient and mouse kidney samples.
Main Results:
- 140 human and 160 murine TRFs were identified as dysregulated.
- Enriched pathways included Janus kinase/Signal transducer and activator of transcription (JAK-STAT), Tumor Necrosis Factor (TNF), and Transforming Growth Factor-beta (TGF-β) signaling.
- Three novel TRFs (Prohibitin, RFX1, ADNP) were significantly dysregulated in obstructed kidneys.
Conclusions:
- This study uncovers critical TRFs in obstructed kidneys, advancing our understanding of pediatric obstructive nephropathy.
- The findings provide novel molecular insights into the pathogenesis of kidney injury.
Background:
Obstructive nephropathy is one of the leading causes of kidney injury in infants and children. Increasing evidence has shown that transcription-related factors (TRFs), including transcription factors and cofactors, are associated with kidney diseases. However, a global landscape of dysregulated TRFs in pediatric patients with obstructive nephropathy is lacking.
Methods:
We mined the data from our previous proteomic study for the TRF profile in pediatric patients with obstructive nephropathy and unilateral ureteral obstruction (UUO) mice. Gene ontology (GO) analysis was performed to determine pathways that were enriched in the dysregulated TRFs. We then took advantage of kidney samples from patients and UUO mice to verify the selected TRFs by immunoblots.
Results:
The proteomes identified a total of 140 human TRFs with 28 upregulated and 1 downregulated, and 160 murine TRFs with 88 upregulated and 1 downregulated (fold change >2 or <0.5). These dysregulated TRFs were enriched in the inflammatory signalings, such as janus kinase/signal transducer and activator of transcription (JAK-STAT) and tumor necrosis factor (TNF) pathways. Of note, the transforming growth factor (TGF)-β signaling pathway, which is the master regulator of organ fibrosis, was enriched in both patients and mice. Cross-species analysis showed 16 key TRFs that might mediate obstructive nephropathy in patients and UUO mice. Moreover, we verified a significant dysregulation of three previously unexplored TRFs; prohibitin (PHB), regulatory factor X 1 (RFX1), and activity-dependent neuroprotector homeobox protein (ADNP), in patients and mice.
Conclusions:
Our study uncovered key TRFs in the obstructed kidneys and provided additional molecular insights into obstructive nephropathy.
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