Abstract: PO2493
Calponin 2 Determines AKI to CKD Transition Through Alternating Fatty Acid Oxidation
Session Information
- CKD: Metabolism, Epigenetics, and Signaling
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2103 CKD (Non-Dialysis): Mechanisms
Authors
- Gui, Yuan, University of Connecticut School of Medicine, Farmington, Connecticut, United States
- Zhou, Dong, University of Connecticut School of Medicine, Farmington, Connecticut, United States
Background
Calponin 2 (CNN2) is an actin filament-associated regulatory protein that plays a central role in numerous fundamental biological processes, including cell proliferation, motility, and adhesion to substrates and others cells. Emerging evidence suggests that cell mechanics can have direct, non-transcriptional influences on cell metabolism. The kidney is a highly metabolically active organ. Fatty acid oxidation is one of the major metabolic processes that occurred in the kidney under pathophysiological conditions. It remains unknown whether CNN2 plays a role in mediating kidney disease progression from the perspective of cell metabolism.
Methods
We constructed ischemic reperfusion injury (IRI) and unilateral ureter obstruction (UUO) animal models in this study. In vitro and in vivo translational experiments and proteomics were performed.
Results
Our quantitative proteomics revealed that CNN2 was induced at 1d and peaked at 10d after ischemic injury. In AKI or CKD patients' kidney biopsy specimens, CNN2 expression was markedly induced and predominantly localized in the interstitial compartment. In vivo, knockdown CNN2 significantly preserved kidney function after ischemic AKI at 1 day. In two classic CKD models induced by 10-d IRI or 7-d UUO, the mice with CNN2 knockdown exhibited reduced expression of fibronectin, α-SMA, and collagen type I, compared to controls. In the meantime, Oil-Red staining showed reduced lipid accumulation in CNN2 knockdown mice kidneys than in controls. Mechanistically, we revealed that knockdown CNN2 could promote fatty acid oxidation to repair injured kidneys and subsequently halt disease progression, as assessed by the increased expression of PPARα, CPT1α, and ACOX1.
Conclusion
Our findings suggested that CNN2 is a crucial determinant in mediating the transition from AKI to CKD through alternating fatty acid oxidation.
Funding
- NIDDK Support