Abstract: FR-PO972
Detection of Autotaxin and Lysophosphatidic Acid Receptors in Glomerular Diseases within Glomerulus
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
- Kumagai, Naonori, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Hirayama, Masaya, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Ando, Takuma, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Kondo, Tomomi, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Matsumoto, Yuji, Fujita Ika Daigaku, Toyoake, Aichi, Japan
- Ikezumi, Yohei, Fujita Ika Daigaku, Toyoake, Aichi, Japan
Background
Lysophosphatidic acid (LPA) is a lysophospholipid that acts as a chemical mediator. It acts through six dedicated receptors, LPA receptor 1-6 (LPAR1-6). LPA is mainly produced by autotaxin (ATX) in blood from lysophospholipids in blood as a substrate. Moreover, LPA is produced by mPA-PLA within cells from phosphatidic acid in the cells as a substrate. be. The Pathophysiological role of the LPA and ATX in glomerular diseases within glomerulus remains unclear.
Methods
Immunostaining for LPAR1-5 and ATX was performed on renal biopsy specimens of pediatric glomerular diseases such as lupus nephritis, membranous nephropathy, idiopathic nephrotic syndrome, IgA nephropathy, and mesangioproliferative glomerulonephritis (MPGN). Moreover, ATX mRNA was detected by in situ hybridization.
Results
LPAR1-5 and ATX were strongly stained in lupus nephritis and membranous nephropathy. They were stained negative to weakly positive in the other glomerular diseases. ATX mRNA was detected in mesangial cells in IgA nephropathy and MPGN, however, was hardly detected in lupus nephritis and membranous nephropathy.
Conclusion
In systemic lupus erythematosus and lupus nephritis, ATX is assumed to be produced in macrophage and released into blood, resulting in elevated concentration in blood and urine. Taken together with the present study, these findings imply that in systemic lupus erythematosus and lupus nephritis ATX in blood is deposited in the glomerulus and LPA is produced in situ. Produced LPA acts in an autocrine and/or paracrine manner through LPA receptors and are involved in pathophysiological role. Conversely, in IgA nephropathy and MPGN, ATX is produced in situ within the glomerulus and is involved in the pathophysiological role. It is needed to elucidate the pathophysiological role of LPA and ATX in each glomerular disease within glomerulus.
Funding
- Government Support – Non-U.S.