Kidney Week

Abstract: FR-PO963

Long Noncoding RNA Associated with Exacerbation of IgA Nephropathy by Exposure to Fine Particulate Matter

Session Information

• Pathology and Lab Medicine - 1
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Pathology and Lab Medicine

• 1800 Pathology and Lab Medicine

Authors

• Song, Daun, Konyang University Hospital, Daejeon, Korea (the Republic of)

Daun Song, MD

• Lee, Ji won, Konyang University Hospital, Daejeon, Korea (the Republic of)

Ji won Lee, MD

• Yoon, Se-Hee, Konyang University Hospital, Daejeon, Korea (the Republic of)

Se-Hee Yoon, MD, PhD

• Yun, Sung-Ro, Konyang University Hospital, Daejeon, Korea (the Republic of)

Sung-Ro Yun, MD, PhD

• Hwang, Won Min, Konyang University Hospital, Daejeon, Korea (the Republic of)

Won Min Hwang, MD, PhD

• Park, Yohan, Konyang University Hospital, Daejeon, Korea (the Republic of)

Yohan Park, MD

Group or Team Name

• Div of Nephrology, Dept of Internal Medicine.

Background

The pathophysiology of IgA nephropathy has been extensively elucidated. However, little is known about long non-coding RNAs (lncRNAs) associated with exacerbation of IgA nephropathy. Fine particulate matter is a significant emerging environmental issue, yet its impact on the exacerbation of IgA nephropathy has not been studied. This study aims to investigate the exacerbation of IgA nephropathy by exposure to fine particulate matter and to explore the associated lncRNAs in a spontaneous IgA nephropathy animal model.

Methods

This study used high serum IgA (HIGA) mice as disease group and BALB/c mice as control group, with a total of twelve 8-week-old mice divided into fine particulate matter exposure groups (HIGA-E:3, BALB/c-E:3) and non-exposure groups (HIGA-NE:3, BALB/c-NE:3). Fine particulate matter exposure was conducted using a sealed cage system, with exposure for 1 hour at a time, 5 times a week, for 12 weeks. The mice were sacrificed at 24 weeks of age. B-cells were separated from the spleen using magnetic-activated cell sorting. RNA isolation was performed from the extracted live B-cells, and total RNA sequencing was conducted.

Results

Regardless of exposure, the HIGA groups had significantly higher serum IgA levels compared to the BALB/c groups. IgA lectin binding assays showed higher levels of glycosylated IgA in the HIGA-NE than in the HIGA-E group, suggesting higher levels of pathologic IgA in the HIGA-E group. Increased expressions of toll-like receptor (TLR)-9 were observed in the lungs of BALB/c-E and HIGA-E groups, with significantly elevated serum APRIL and BAFF levels in the HIGA-E group. Kidney pathology results showed the strongest mesangial IgA deposit and the highest renal injury score in the HIGA-E, followed by the HIGA-NE group (7.7±0.6 vs. 5.3±0.6, P=0.043). Splenic B-cell RNA sequencing revealed more than a two-fold decrease in the expression of specific lncRNAs (Gm54045, Chaserr, LOC115487771, 2310058N22Rik) in the HIGA-E compared to the HIGA-NE group.

Conclusion

Fine particulate matter increases lung TLR-9 expression, leading to elevated BAFF, APRIL, and pathologic IgA levels, and exacerbates IgA nephropathy in the HIGA mice. This exacerbation is associated with a decrease in specific lncRNAs in splenic B-cells, suggesting these lncRNAs may serve as potential therapeutic or diagnostic targets.