NAT10-ac4C axis promote renal fibrosis. NAT10-ac4C axis promote renal fibrosis

RNA modification play vital roles in renal fibrosis. However, whether ac4C modification functions in renal fibrogenesis remains unknown. Here, we found that NAT10-ac4C axis plays pro—fibrotic role in kidney. ac4C RIP sequencing demonstrated NAT10-ac4C axis functions via regulating multiple master genes of exosome secretion in tubular epithelial cells. In summary, targeting NAT10-ac4C axis is a promising strategy for renal fibrosis. Overall design: Wild-type HK-2 cells and NAT10 KD HK-2 cells were used for ac4C-RIP-seq.

RNA修饰在肾纤维化中发挥至关重要的作用。然而，N4-乙酰胞嘧啶（ac4C）修饰在肾纤维化发生过程中的功能尚不清楚。本研究发现，N-乙酰基转移酶10（NAT10）-ac4C轴在肾脏中具有促纤维化作用。ac4C RIP测序结果显示，该轴可通过调控肾小管上皮细胞中外泌体分泌的多个核心基因发挥功能。综上，靶向NAT10-ac4C轴是治疗肾纤维化的极具潜力的策略。实验设计：以野生型HK-2细胞及NAT10敲低HK-2细胞为实验材料，开展ac4C-RIP测序实验。