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Abstract: SA-PO454

Renovascular Disease Induces Mitochondrial Damage and Impairs the Reparative Capacity of Swine Scattered Tubular-Like Cells

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine

Authors

  • Aghajani Nargesi, Arash, Mayo Clinic, Rochester, Minnesota, United States
  • Zhu, Xiang yang, Mayo Clinic, Rochester, Minnesota, United States
  • Conley, Sabena, Mayo Clinic, Rochester, Minnesota, United States
  • Woollard, John R., Mayo Clinic, Rochester, Minnesota, United States
  • Saadiq, Ishran M., Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo Clinic College of Medicine, Rochester, Minnesota, United States
  • Eirin, Alfonso, Mayo Clinic, Rochester, Minnesota, United States
Background

Scattered tubular-like cells (STC) contribute to repair neighboring injured renal tubular cells. Mitochondria mediate STC biology and function, but might be injured by the ambient milieu. We hypothesized that the microenviroment induced by the ischemic and metabolic components of renovascular disease (RVD) impairs STC mitochondrial structure and function in swine, which can be attenuated with mitoprotection.

Methods

CD24+/CD133+ STCs were quantified in pig kidneys after 16 weeks of metabolic syndrome (MetS) or Lean diet with or without renal artery stenosis (RAS) (n=6 each). Pig STC were isolated and characterized, and mitochondrial structure and membrane potential were assessed in cells untreated or incubated with the mitoprotective drug elamipretide (ELAM, 1nM for 6hrs). STC protective effects were assessed in-vitro by their capacity to improve viability of injured pig tubular epithelial (PK1) cells.

Results

The percentage of STC was higher in MetS, Lean+RAS, and MetS+RAS kidneys compared to Lean (Fig. A). STC isolated from Lean+RAS and MetS+RAS pigs showed decreased mitochondrial matrix density and membrane potential, which were both restored by mitoprotection (Fig. B). Furthermore, mitoprotection improved the capacity of MetS+RAS-STC to repair injured tubular cells in-vitro (Fig. C).

Conclusion

RVD in swine is associated with a higher percentage of STC, which was predominantly affected by MetS. Ischemia induces structural and functional alterations in STC mitochondria, which can be attenuated by mitoprotection. These observations suggest a key role for mitochondria in the renal reparative capacity of STC.

Funding

  • NIDDK Support