Abstract: PO1831
Mitochondrial Injury May Be a Ubiquitous Finding in the Pathogenesis of Various Glomerulonephritis
Session Information
- Glomerular Diseases: IgA, C3G, and FSGS
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Yu, Byung chul, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
- Park, Moo Yong, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
- Choi, Soo Jeong, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
- Kim, Jin kuk, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
- Hwang, Seung Duk, Division of Nephrology, Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Bucheon, Gyeonggi-do, Korea (the Republic of)
Background
Previous study showed that mitochondrial injury is associated with IgA nephropathy (IgAN). It is not clear whether mitochondrial injury is a unique finding in IgAN or a ubiquitous finding in various glomerulonephtiris (GN). To clarify this, we analyzed urinary mitochondrial DNA (mtDNA) levels and expression of the stimulator of interferon genes (STING) pathway activated by mtDNA leakage in various GN.
Methods
We prospectively enrolled age-sex matched healthy volunteers (HV) and biopsy-proven IgAN, minimal change disease (MCD), acute tubulointerstitial nephritis (ATIN), and minor glomerular abnormalities (MGA) (n=30, 8, 10, and 7 each, respectively). Urinary copy number of the mtDNA genes cytochrome-c oxidase-3 (COX3) and nicotinamide adenine dinucleotide dehydrogenase subunit-1 (ND1) were measured by quantitative polymerase chain reaction. We analyzed STING expression in prostatic cancer specimen as control and kidney tissues obtained from each GN patients by immunohistochemistry staining.
Results
log10ND1/nDNA and log10COX3/nDNA were significantly higher in IgAN (p<0.001, p=0.002), MCD (p<0.001, both), ATIN (p<0.001, both), and MGA (p<0.001, both) compared with HV (Figure 1). Although there was a difference in signal intensity and site of kidney structures, positive staining for STING was observed in the kidney tissue of each GN patients. Characteristically, STING was strongly stained in the tubulointerstitium for ATIN and in the distal tubule for MGA (Figure 2).
Conclusion
Elevated urinary mtDNA copy numbers and STING activation were observed in various GN. These results suggest that mitochondrial injury would be a ubiquitous finding in the pathogenesis of various GN.
Funding
- Government Support - Non-U.S.