Poricoic acid a ameliorates high glucose-induced podocyte injury by regulating the AMPKα/FUNDC1 pathway

被引:0
作者
Wu, Yuwen [1 ]
Xu, Yancheng [1 ]
Deng, Haohua [1 ]
Sun, Jiazhong [1 ]
Li, Xin [1 ]
Tang, Jun [1 ]
机构
[1] Wuhan Univ, Dept Endocrinol, Zhongnan Hosp, 167 Donghu Rd, Wuhan 430071, Hubei, Peoples R China
关键词
AMPK alpha; Diabetes; Diabetic kidney disease; FUNDC1; Podocyte; Poricoic acid A; DIABETIC-NEPHROPATHY; AMPK; SUPPRESSION; MECHANISMS; AUTOPHAGY;
D O I
10.1007/s11033-024-09921-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
BackgroundPoricoic acid A (PAA), a major triterpenoid component of Poria cocos with anti-tumor, anti-fibrotic, anti-inflammatory, and immune-regulating activities, has been shown to induce podocyte autophagy in diabetic kidney disease (DKD) by downregulating FUN14 domain containing 1 (FUNDC1). This study aimed to identify the role of adenosine monophosphate-activated protein kinase alpha (AMPK alpha) in PAA-mediated phosphorylation of FUNDC1 in podocyte injury occurring in the pathogenesis of DKD.Methods and resultsA cellular model of renal podocyte injury was established by culturing MPC5 cells under high-glucose (HG) conditions. MPC5 cells were subjected to transfection with small interfering RNA (siRNA) targeting AMPK alpha or siRNA targeting FUNDC1, an AMPK alpha activator, or PAA. PAA treatment induced the phosphorylation of AMPK alpha in HG-cultured podocytes. AMPK alpha activation was implicated in the inhibitory effect of PAA on FUNDC phosphorylation in HG-cultured podocytes. Treatment targeting the AMPK alpha activator also significantly augmented proliferation, migration, mitochondrial membrane potential, and autophagy levels, while reducing apoptosis levels, inhibiting oxidative stress, and suppressing the release of proinflammatory factors in HG-cultured MPC5 cells. In contrast, insufficient expression of AMPK alpha reversed the effects of PAA on the proliferation, migration, and apoptosis of podocytes and further exacerbated the reduction of phosphorylated FUNDC1 expression in podocytes under HG conditions.ConclusionsAMPK alpha is involved in the regulation of FUNDC1 phosphorylation by PAA in HG-induced podocyte injury. Furthermore, the AMPK alpha/FUNDC1 pathway plays a crucial regulatory role in HG-induced podocyte injury. These findings support AMPK alpha, FUNDC1, and the AMPK alpha/FUNDC1 pathway as targets for PAA intervention.
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页数:14
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