Kidney Week

Abstract: TH-PO650

Metabolic Syndrome and Renal Artery Stenosis Induce Mitochondrial Damage in Swine Scattered Tubular Cells

Session Information

• Development, Stem Cells, Regenerative Medicine - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

• Aghajani Nargesi, Arash, Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Arash Aghajani Nargesi,

• Zhu, Xiang yang, Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Xiang yang Zhu,

• Saadiq, Ishran M., Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Ishran M. Saadiq,

• Lerman, Amir, Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Amir Lerman,

• Lerman, Lilach O., Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Lilach O. Lerman,

• Eirin, Alfonso, Mayo Clinic Rochester MN, Rochester, Minnesota, United States

Alfonso Eirin,

Background

Scattered tubular cells (STC) are considered to contribute to repair neighboring injured renal tubular epithelial cells. Mitochondria mediate STC biology and function, by producing energy and modulating redox status. We hypothesized that kidney injury due to coexisting metabolic syndrome (MetS) and renal artery stenosis (RAS) in swine impairs STC mitochondrial structure and function, which can be attenuated with mitoprotection.

Methods

CD24+/CD133+ STC (Fig. A) were isolated from pig kidneys after 16wks of MetS or Lean diet with or without RAS (n=7 each). Mitochondrial structure (electron microscopy), membrane potential (TMRE staining), and oxidative stress (Mito-SOX staining) were assessed in STC untreated or incubated with the mitoprotective drug elamipretide (ELAM, 1nM for 6hrs).

Results

Mitochondrial area increased and matrix density decreased in Lean+RAS- and MetS+RAS-STC compared to Lean- and MetS-STC, but both were restored in ELAM-treated pigs (Fig. B-C). Mitochondrial membrane potential diminished and mitochondrial production of reactive oxygen species increased in MetS-, Lean+RAS-, and MetS+RAS-STC, but reversed after treatment with ELAM (Fig. D-E).

Conclusion

Coexisting MetS and RAS induce structural and functional alterations in swine STC mitochondria, which might limit their regenerative potential. These observations suggest a potential role for mitoprotection in preserving the renal reparative capacity of STC.

Funding

• NIDDK Support –