Abstract: PO1412
Tissue MALDI-Mass Spectrometry Imaging Reveals the Potential Role of PLPP3 in Regulating Lysophosphatidic Acid Signaling in Aging Kidney
Session Information
- Glomerular Diseases: Fibrosis and Extracellular Matrix
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix
Authors
- Liu, Li, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Pamreddy, Annapurna, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Gao, Jingli, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Min, Liang, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Lee, Hak Joo, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Drel, Viktor, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Chen, Wei, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Geng, Hui, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Liu, Ya guang, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Kasinath, Balakuntalam S., The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Sharma, Kumar, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
- Zhang, Guanshi, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
Background
Increasing evidence suggests that accumulation of lysophosphatidic acid (LPA) and aberrant activation of LPA signaling is implicated in various human diseases such as diabetic kidney disease. However, the role of LPA signaling in aging-related kidney injury remains elusive.
Methods
C57BL/6J male mice at 5 months (Control) and 24 months (Aging), N=10/group, were used in the current study. Kidney pathological changes were evaluated based on PAS-stained images and nephropathy markers including urinary albumin creatinine ratio (ACR) and kidney injury molecule-1 (KIM-1). Gene expression and protein levels of major enzymes/effectors involved in LPA metabolism and signaling were measured in kidney cortical tissues using standard RT-qPCR and western blotting approaches. Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was performed for spatial lipidomics analysis of lipids including LPA and other species in kidneys of aging mice and controls. MetaboAnalyst and GraphPad were employed for statistical analyses.
Results
Histological images showed that aging kidney developed glomerulosclerosis at the age of 24 months. Aging mice also had higher levels of urinary albumin, ACR, and KIM-1. Interestingly, both mRNA and protein levels of phospholipid phosphatase 3 (PLPP3), an enzyme that can dephosphorylate and inactivate the signaling functions of LPA, were lower in renal cortical tissues of aging mice. The gene expression level of LPA receptor 1 (LPAR1) was upregulated in aging renal cortical tissues. In addition, oscillations of gene expression and protein levels of enzymes involved in LPA metabolism/signaling, mitochondrial biogenesis, and mitochondrial dynamics were observed in aging kidneys. In the MALDI-MSI analysis, we found altered sphingolipid metabolism in glomeruli of mouse aging kidneys compared with controls. In particular, several LPA (e.g., LPA (16:0)) species were increased in aging glomeruli, suggesting the potential role of LPA signaling in the aging kidney.
Conclusion
These findings suggest that reduced PLPP3 contributes to the accumulation of LPA in glomeruli of aging kidneys. Activation of LPA signaling in glomeruli may play an important role in the pathogenesis of aging-related kidney injury.
Funding
- NIDDK Support