The regulation of LPCAT3 by miR-124-3p.1 in acute kidney injury suppresses cell proliferation by disrupting phospholipid metabolism

Sepsis-associated acute renal injury (SA-AKI) is a common critical clinical disease. It is associated with increased mortality and increased risk of progression to chronic kidney disease. However, its patho-genesis is not fully known. We hypothesized that metabolic interactions mediate cell apoptosis and AKI. We found that phosphatidylcholine content in human renal tubular epithelial cells following lipopolysaccharide-induced injury was increased. The activity of lysophosphatidylcholine acyltransferase 3 (LPCAT3), a key enzyme in phospholipid metabolism, was increased, while the expression of miR-124-3p.1, which targets LPCAT3, was decreased. We also found that in the serum of SA-AKI patients, LPCAT3 activity was increased, and miR-124-3p.1 expression was decreased. Further experiments confirmed the specific binding of exocrine miR-124-3p.1 to LPCAT3. Our data reveal the molecular mechanisms of phospholipid metabolic disorder in early SA-AKI as well as the role of the miR-124-3p.1/LPCAT3 pathway in SA-AKI, which leads to ferroptosis. These results could provide the scientific basis for early diagnosis and renal replacement therapy in SA-AKI.(c) 2022 Elsevier Inc. All rights reserved.

Automated summary

Phospholipid metabolic disorder plays a crucial role in the development of SA-AKI. The increased activity of LPCAT3 and decreased expression of miR-124-3p.1 may lead to ferroptosis. These findings contribute to the early diagnosis and renal replacement therapy for SA-AKI.