Kidney Week

Abstract: FR-PO1121

Ferroptosis of Kidney After SARS-CoV-2 Infection

Session Information

• COVID-19 - II
  November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Coronavirus (COVID-19)

• 000 Coronavirus (COVID-19)

Authors

• Park, Woong, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)

Woong Park,

• Jung, Yujin, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)

Yujin Jung,

• Kim, Hyeongwan, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)

Hyeongwan Kim,

• Yeom, Jihyun, Jeonbuk National University Hospital, Jeonju, Jeollabuk-do , Korea (the Republic of)

Jihyun Yeom,

• Lee, Soo jin, Jeonbuk National University Hospital, Jeonju, Jeollabuk-do , Korea (the Republic of)

Soo jin Lee,

• Shin, Yujin, Jeonbuk National University Hospital, Jeonju, Jeollabuk-do , Korea (the Republic of)

Yujin Shin,

• Kim, Won, Jeonbuk National University Medical School, Jeonju, Jeollabuk-do , Korea (the Republic of)

Won Kim,

Background

Although kidney involvement have been evaluated for human Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection, none have fully evaluated the ferroptosis in the kidney after SARS-CoV-2 infection. Here, we evaluate the ferroptotic renal injury in the transgenic mice expressing the human ACE2 receptor driven by the cytokeratin-18 gene promoter (K18-hACE2) after SARS-CoV-2 infection.

Methods

To investigate the effect of SARS-CoV-2 on renal ferroptosis, we administered 2.5 x 10⁴ p.f.u. SARS-CoV-2 via intranasal to K18-hACE2 mice. After 7 days SARS-CoV-2 infection, kidney tissues were harvested. SARS-CoV-2 infection and ferroptosis were evaluated by immunohistochemistry. Next, ferroptosis-related markers, glutathione peroxidase 4(Gpx4), prostaglandin-endoperoxide synthase 2(Ptgs2), Acyl-CoA synthetase long chain family member 4(Acsl4), nuclear factor erythroid-2-related factor 2(Nrf2), heme oxygenase-1(Ho-1), transferrin receptor 1(Tfr1), ferritin heavy chain 1(Fth1) and nuclear receptor coactivator 4(Ncoa4) were evaluated by quantitative PCR.

Results

SARS-CoV-2 infection significantly increase the expression of SARS-CoV-2 spike protein in the tubular epithelial cells of the renal cortex and medulla. Protein expression of GPX4 was significantly decreased in the renal medulla. In the kidney of SARS-CoV-2-infected mice, the ferritin-related markers ferritin heavy chain 1(FTH1) and transferrin receptor 1(TFR1) and lipid peroxidation marker, dihydroethidium (DHE) were also increased in histological experiments. Next, the mRNA levels of Ptgs2, Acsl4, Nrf2, Ho-1, Fth1 and Ncoa4 were increased in the kidneys of SARS-CoV-2 infected mice compared to non-infected mice.

Conclusion

All of our data suggest that SARS-CoV-2 infection shares many features of ferroptosis in the kidney and can be used to define the ferroptosis of kidney injury and antiviral-based countermeasures in COVID-19 infection.

Funding

• Government Support – Non-U.S.