#5349 CYCLIN D1 AMELIORATES ACUTE KIDNEY INJURY BY IMPROVING FATTY ACID OXIDATION VIA AMPK PATHWAY

Abstract Background and Aims Acute kidney injury (AKI) is a life-threatening condition. The absence of oxygen during the acute ischemic phase would disturb energy metabolism cause tubular epithelial cell damage. Fatty Acid Oxidation (FAO) main source production renal proximal cells. Timely promoting FAO, increasing supplies energy, proliferation are essential to improve injury, but there no clinically recognized effective treatment for this. Cyclin D1(CCND1), member cycle family, plays vital role in proliferation. Our previous study found that CCND1 improved AKI accompanied with increased fatty acid oxidation. Therefore, we investigated molecular basis involvement oxidation AKI. Method was evaluated human cells (HK-2 cells) male C57BL/6J mice (wild type). protective mouse model ischemia-reperfusion treated by ultrasound-microbubble-mediated kidney-specifically transferring CCND1-expressing plasmids Eight-week-old type) were subjected bilateral artery occlusion 30min followed 24h reperfusion. We proliferation, autophagy vitro vivo. In addition, concentrations blood urea nitrogen creatinine, ultrastructure so on. Results vivo studies had shown activation can prevent AKI-induced lipid accumulation, tubule function declined after injury. Compared test control, significantly (p < 0.05) lowered creatinine. Kidney specific overexpression promoted reduced apoptosis. Mechanistically, activated AMPK pathway, which expression phosphorylation AMP protein kinase (p-AMPK) upregulated FAO. On contrary, inhibiting exacerbated impairment FAO disturbed metabolism. Conclusion Thus, accumulation via active pathway (PTECs). Hence, reconstruction may be novel therapeutic strategy treating