Affiliation:
1. Department of Nephrology Shandong Provincial Hospital Affiliated to Shandong First Medical University Jinan China
2. Department of Nephrology Shandong Provincial Hospital, Shandong University Jinan China
Abstract
AbstractDiabetic kidney disease (DKD) is one of the severe complications of diabetes mellitus, yet there is no effective treatment. Exploring the development of DKD is essential to treatment. Podocyte injury and inflammation are closely related to the development of DKD. However, the mechanism of podocyte injury and progression in DKD remains largely unclear. Here, we observed that FTO expression was significantly upregulated in high glucose‐induced podocytes and that overexpression of FTO promoted podocyte injury and inflammation. By performing RNA‐seq and MeRIP‐seq with control podocytes and high glucose‐induced podocytes with or without FTO knockdown, we revealed that serum amyloid A2 (SAA2) is a target of FTO‐mediated m6A modification. Knockdown of FTO markedly increased SAA2 mRNA m6A modification and decreased SAA2 mRNA expression. Mechanistically, we demonstrated that SAA2 might participate in podocyte injury and inflammation through activation of the NF‐κB signaling pathway. Furthermore, by generating podocyte‐specific adeno‐associated virus 9 (AAV9) to knockdown SAA2 in mice, we discovered that the depletion of SAA2 significantly restored podocyte injury and inflammation. Together, our results suggested that upregulation of SAA2 promoted podocyte injury through m6A‐dependent regulation, thus suggesting that SAA2 may be a therapeutic target for diabetic kidney disease.
Funder
National Natural Science Foundation of China
Department of Science and Technology of Shandong Province
Taishan Scholar Project of Shandong Province
Cited by
1 articles.
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