Abstract: TH-PO0557
Sterile Inflammation Plays a Crucial Role in Adult Zebrafish Kidney Regeneration
Session Information
- Development, Stem Cells, and Regenerative Medicine
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Development, Stem Cells, and Regenerative Medicine
- 600 Development, Stem Cells, and Regenerative Medicine
Authors
- Olajuyin, Olaleye, University of Maine System, Bangor, Maine, United States
- Schenk, Heiko Joachim, Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States
- Sampson, William, University of Maine System, Bangor, Maine, United States
- Kamei, Caramai Nanae, Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States
- Drummond, Iain A., Mount Desert Island Biological Laboratory, Salsbury Cove, Maine, United States
Background
Kidney disease affects over 35 million Americans and has become a significant global health challenge. The shortage of organ donors, combined with the rising number of patients waiting for transplants, has intensified the search for alternative therapies. Zebrafish have a remarkable kidney regeneration capacity due to persistence of renal stem cells in the adult, however, the mechanisms of stem cell activation after injury remain unknown.
Methods
Using RNA-seq, we found that acute kidney injury induced by gentamicin injection resulted in a robust inflammatory response in enzymatically isolated kidney tubule cells at two days post-injury, which correlated with the expression of known markers of kidney tubule injury. To investigate whether inflammation alone, without physical injury, could promote kidney regeneration in adult zebrafish we administered intraperitoneal injections of various immune activators, including lipopolysaccharide, Zymosan, and polyinosinic: polycytidylic acid.
Results
The induction of inflammation was confirmed by the upregulation of pro-inflammatory cytokines such as il-6, tnfa, and il-1b, as well as the antiviral response marker mxa and the proliferation-associated gene pim-1, all of which play key roles in modulating immune responses and cell proliferation. To confirm the absence of kidney injury, we demonstrated that Kidney Injury Molecule-1 (kim-1) and slc20a1a expression were not significantly changed in treated fish. Seven days post-injection, we observed the formation of lhx1a+ new nephrons in the adult zebrafish kidneys using in-situ hybridization, qPCR, and immunostaining techniques. Additionally, EdU incorporation assays revealed active proliferation within these newly formed nephrons. LPS-induced new nephrons developed glomeruli and were functional in labelled dextran filtration assays.
Conclusion
These findings demonstrate that inflammation alone, independent of physical injury, is sufficient to activate progenitor cell-based kidney regeneration in adult zebrafish. This study suggests that sterile inflammation is the initial signal for kidney regeneration in zebrafish and provides novel insights into the role of inflammation in regenerative processes.
Funding
- NIDDK Support