Abstract: TH-PO406
Deciphering Cellular Mechanisms in Cells of Renin Lineage-Mediated Kidney Regeneration under SGLT2 Inhibition
Session Information
- Development, Organoids, Injury, and Regeneration
October 24, 2024 | 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
- van der Pluijm, Loïs, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- de Klerk, Juliette A., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- Koudijs, Angela, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- Rotmans, Joris I., Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- Gross, Kenneth W., Roswell Park Comprehensive Cancer Center, Buffalo, New York, United States
- Pieper, Michael P., Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riss, Baden-Württemberg, Germany
- Van Zonneveld, Anton Jan, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
- Bijkerk, Roel, Leids Universitair Medisch Centrum, Leiden, Zuid-Holland, Netherlands
Group or Team Name
- Einthoven Laboratory for Vascular and Regenerative Medicine.
Background
A newly discovered, promising source of renal intrinsic regenerative cells comprise the cells of renin lineage (CoRL). Juxtaglomerular CoRL can repopulate essential glomerular cells like podocytes and mesangial cells post-injury, a process that can be enhanced by inhibiting the sodium glucose co transporter 2 (SGLT2). Despite its potential, the underlying cellular mechanisms remain largely elusive. Our study aims to identify the key genes driving this reparative process.
Methods
We employed a chronic kidney disease (CKD) model of 5/6 nephrectomy (5/6NX) in Ren1cre-tdTomato CoRL-lineage trace mice while daily administering the SGLT2 inhibitor empagliflozin (10mg/kg) for two weeks. Renal CoRL were isolated using fluorescent automated cell sorting (FACS) and subjected to single cell RNA sequencing.
Results
As determined by blood urea levels and GFR measurements throughout the study, we demonstrated enhanced kidney function recovery upon SGLT2 inhibition post kidney injury. In addition, SGLT2 inhibition led to increased numbers of CoRL-derived intraglomerular cells, specifically due to a rise in CoRL-derived podocytes. Single-cell RNA sequencing of CoRL revealed several distinct cell type clusters and confirmed the presence of a CoRL-derived podocyte cluster. Currently, pseudo-time trajectory analyses are being conducted to further elucidate differentiation dynamics of CoRL, particularly under SGLT2 inhibition.
Conclusion
Our findings highlight the potential of SGLT2 inhibition in promoting CoRL-mediated intrinsic kidney regeneration. Ongoing investigations aim to further decode the gene expression patterns during the phenotypic commitment shift of CoRL post-injury under SGLT2 inhibition. These insights may pave the way for novel, targeted approaches to augment the kidney’s regenerative capacity.
Funding
- Commercial Support – Boehringer Ingelheim