Abstract: FR-PO678
Dihydroartemisinin Inhibits Mesangial Cell Proliferation in IgA Nephropathy by Regulating PGC1α-Mediated Glycometabolism
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
- Xia, Ming, Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, State..., China
- Zhao, Juanyong, Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, State..., China
- Fan, Xinyan, Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, State..., China
- Tang, Xunzi, Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, State..., China
- Liu, Hong, Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, State..., China
Background
Mesangial cell proliferation is the basic pathological feature of IgA nephropathy (IgAN), but the mechanism of glucose metabolism in mesangial cell proliferation has not been studied. It has been reported that artemisinin analogues can effectively regulate cellular glucometabolic enzymes and improve autoimmune diseases, but their efficacy on IgAN remains unclear. The aim of this study was to clarify the changes of glucose metabolism in IgAN, and to explore the therapeutic effect of dihydroartemisinin (DHA) on IgAN.
Methods
The expression of glucometabolic enzymes, and the relationship between enzymes and clinicopathology in IgAN patients were analyzed using GEO datasets and renal biopsy specimens. The expression of glucometabolic enzymes, energy metabolic pathway, cell proliferation, apoptosis were evaluated in mesangial cells after PGC1α agonist/ inhibitor/DHA intervention. Enrichment pathways was analyzed and the metabolites of glucose metabolism were detected after DHA intervention. The IgAN mouse model was administrated with DHA, renal function and pathology, as well as the expression level of glucometabolic enzymes in glomeruli were detected.
Results
The expression of glycolytic enzyme HK1 was increased, and the expression of gluconeogenic enzyme (PCK1, FBP1) were decreased in IgAN glomeruli. The expression of glycometabolic enzymes were significantly correlated with renal clinical indicators. PGC1α was significantly correlated with differentially expressed glucometabolic enzymes, and its expression was lower in IgAN patients with heavy mesangial cell proliferation. DHA upregulated PGC1α expression, inhibited glycolysis and suppressed mesangial cell proliferation. In vivo, DHA reversed the expression of glucometabolic enzymes and alleviated kidney injury in IgAN mice.
Conclusion
This study demonstrated the alteration of glucose metabolism in glomeruli, and the therapeutic effects of DHA in regulation of PGC1α and glucose metabolism in IgAN. These results provide new strategies for renal protection, as well as theoretical basis and intervention targets for DHA therapy of IgAN.
Funding
- Other NIH Support