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Abstract: SA-OR04

SARS-CoV-2 Receptor Networks in Diabetic Kidney Disease, BK Virus Nephropathy, and COVID-19 Associated AKI

Session Information

Category: Coronavirus (COVID-19)

  • No subcategory defined

Authors

  • Menon, Rajasree, University of Michigan, Ann Arbor, Michigan, United States
  • Otto, Edgar A., University of Michigan, Ann Arbor, Michigan, United States
  • Sealfon, Rachel S., Flatiron Institute, New York, New York, United States
  • Nair, Viji, University of Michigan, Ann Arbor, Michigan, United States
  • Wong, Aaron, Flatiron Institute, New York, New York, United States
  • Theesfeld, Chandra L., Princeton University, Princeton, New Jersey, United States
  • Chen, Xi, Flatiron Institute, New York, New York, United States
  • Wang, Yuan, Princeton University, Princeton, New Jersey, United States
  • Schaub, Jennifer A., University of Michigan, Ann Arbor, Michigan, United States
  • Berthier, Celine C., University of Michigan, Ann Arbor, Michigan, United States
  • Eddy, Sean, University of Michigan, Ann Arbor, Michigan, United States
  • Lienczewski, Chrysta C., University of Michigan, Ann Arbor, Michigan, United States
  • Godfrey, Brad A., University of Michigan, Ann Arbor, Michigan, United States
  • Sohaney, Ryann, University of Michigan, Ann Arbor, Michigan, United States
  • Looker, Helen C., National Institutes of Health, Bethesda, Maryland, United States
  • Mariani, Laura H., University of Michigan, Ann Arbor, Michigan, United States
  • Naik, Abhijit S., University of Michigan, Ann Arbor, Michigan, United States
  • Nelson, Robert G., National Institutes of Health, Bethesda, Maryland, United States
  • Troyanskaya, Olga, Princeton University, Princeton, New Jersey, United States
  • Kretzler, Matthias, University of Michigan, Ann Arbor, Michigan, United States
Background

COVID-19 shows increased disease burden in patients with diabetic kidney disease (DKD). SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for host cell entry, so ACE2 levels may influence SARS-CoV-2 susceptibility. We investigated how pre-existing conditions and drug treatments alter receptor expression in kidney cells (Figure 1).

Methods

Single cell RNA profiling of 7 healthy living donor kidneys, 44 DKD, 3 BK virus nephropathy (BKVN) and a urine COVID19 patient with acute kidney injury (COV-AKI) revealed ACE2 expression primarily in proximal tubular epithelial cells (PTEC).

Results

ACE2 mRNA expression levels were higher in proximal tubule epithelial cells (PTEC) in DKD versus LD, but unaltered by exposures to renin angiotensin aldosterone system inhibitors. Bayesian integrative analysis of public -omics datasets identified molecular network modules induced in ACE2 positive versus negative PTEC in DKD and BKVN (hb.flatironinstitute.org/covid-kidney), that were linked to viral entry, immune activation, endomembrane reorganization, and RNA processing. Similar programs were seen in COV-AKI ACE2-positive PTEC, and overlapped with programs in SARS-CoV-2 infected cells.

Conclusion

A consistent ACE2-coregulated expression program in PTEC may interact with SARS-CoV-2 infection processes. These networks can seed further research into developing therapeutic strategies and assessing risk in patients with COVID-19.

Figure 1: Study overview. Identifying SARS-CoV-2 receptor networks in DKD, BKVN and COV-AKI using scRNAseq and integrative network analyses

Funding

  • NIDDK Support