Abstract: FR-PO679
Spatially Resolved Transcriptomics Reveals Golgi-Endoplasmic Reticulum (ER) Network-Associated Differentially Expressed Genes in Membranous Lupus Nephritis
Session Information
- Glomerular Diseases: From Inflammation to Fibrosis - II
November 03, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Cho, Jeongmin, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Park, Sehoon, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Koh, Jung Hun, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Kim, Yaerim, Keimyung University School of Medicine, Daegu, Korea (the Republic of)
- Han, Seung Seok, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Lee, Hajeong, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
- Kim, Dong Ki, Seoul National University Hospital, Jongno-gu, Seoul, Korea (the Republic of)
Background
Class V lupus nephritis (LN) shares histological similarities with membranous nephropathy (MN) characterized by subendothelial immune complex deposits. However, the differences in pathogenesis between class V LN and other LN classes or anti-PLA2R-associated MN are largely unknown.
Methods
Spatial transcriptomic profiling was conducted using GeoMx Digital Spatial Profiler on formalin-fixed paraffin-embedded kidney biopsy specimens obtained from control (n = 7), LN class I to V (n = 24), and anti-PLA2R-associated MN (n = 16). LN and MN specimens were collected at proteinuric status. Differentially expressed genes (DEGs) between (1) each class of LN (I-V) vs. control and (2) class V LN vs. MN were identified. Gene Ontology (GO) terms for DEGs were annotated using the ToppGene suite.
Results
A total of 128 DEGs were downregulated in class V LN compared to MN. These genes were also downregulated in class V LN when compared to control samples, while no significant expression differences were observed in other LN classes compared to controls. Eleven of 128 downregulated DEGs were annotated with biological process GO terms related to Golgi vesicle transport. Regarding cellular component GO terms, Golgi apparatus (30/128 DEGs), endoplasmic reticulum (ER) membrane (19/128 DEGs), and ER-Golgi intermediate compartment (6/128 DEGs) were among the annotated GO terms associated with the DEGs. DEGs in annotation included GOLGA3, TMED7, BET1L, and RAB10.
Conclusion
The ER-Golgi network and related molecular pathway may be involved in the distinct pathogenesis and clinical features of class V LN.
Figure 1. Visualization of Gene Ontology terms annotated differentially expressed genes