Abstract: PO1712
Compartmental Differences Within the COL3A1 Network in Proteinuric Kidney Disease: Informing Drug Activity Using the Jaccard-Tanimoto Index
Session Information
- Glomerular Diseases: Fibrosis and Extracellular Matrix
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Narayan, Prakash, Angion Biomedica Corp, Uniondale, New York, United States
- Dalapati, Sony, Angion Biomedica Corp, Uniondale, New York, United States
- Zhou, Ping, Angion Biomedica Corp, Uniondale, New York, United States
- Prakash, Natalia, Angion Biomedica Corp, Uniondale, New York, United States
- Pellicano, Anthony, Angion Biomedica Corp, Uniondale, New York, United States
- Goldberg, Itzhak D., Angion Biomedica Corp, Uniondale, New York, United States
Group or Team Name
- Angion Biomedica Corp.
Background
In proteinuric kidney disease, type III collagen (COL III) participates in mesangial expansion, crescent organization, and glomerulosclerosis. Matrix deposition within the tubulointerstitium is associated with worse prognosis. A semi-quantitative analysis was conducted to understand compartmental differences within the COL3A1 transcriptomic network, and to inform therapeutic potential of drugs that mitigate COL III deposition.
Methods
Proteinuria and renal COL3A1 (day 21) mRNA were measured in adult male Wistar rats administered PAN (~100 mg/kg, intraperitoneal). HumanBase was used to build glomerular (G) and tubular (T) COL3A1 transcriptomic networks. Network analysis was restricted to 51 elements each, inclusive of COL3A1, with a minimum interaction confidence of 0.01. The Jaccard-Tanimoto similarity index was used to calculate common elements within the two compartments.
Results
The rat PAN model was associated with increased proteinuria (*, p<0.01 vs. sham) which correlated directly and significantly with renal COL3A1 mRNA expression level. Network analysis revealed a relative strong glomerular COL3A1 interactome with an average strength of 0.8±0.08 and a relatively weaker tubular COL3A1 interactome with an average strength of 0.56±0.01. The Jaccard-Tannimoto similarity index between the glomerular and tubular COL3A1 signaling elements was 5.1%.
Conclusion
Glomerulosclerosis in proteinuric kidney disease may result from a relatively strong COL3A1 transcriptomic network within that compartment. Tubulointerstitial matrix deposition is rare in proteinuric kidney disease, possibly due to a weaker COL3A1 transcriptomic network in that compartment. Drugs designed to specifically mitigate COL III deposition might be most effective against glomerulosclerosis.
Funding
- Other U.S. Government Support