Emodin prevents renal ischemia-reperfusion injury via suppression of CAMKII/DRP1-mediated mitochondrial fission

Wang, Yanqing; Liu, Qian; Cai, Jiaying; Pin, Wu; Wang, Di; Shi, Yundi; Huyan, Tianru; Su, Jing; Li, Xuejun; Wang, Qi; Wang, Hong; Zhang, Fengxue; Bae, Ok‐Nam; Tie, Lu

doi:10.1016/j.ejphar.2021.174603

Cited by 34 publications

(18 citation statements)

References 47 publications

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“…CaMKII is a ubiquitously expressed serine/threonine kinase that plays an important role in diabetic nephropathy [ 26 ] and polycystic kidney diseases [ 5 ]. Several studies have shown that CaMKII activation is involved in cell death, including RTECs [ 4 , 7 , 27 ]. Consistent with these previous studies, we found that CaMKII activity was significantly increased in ADR-treated RTECs in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 99%

CaMKII may regulate renal tubular epithelial cell apoptosis through YAP/NFAT2 in acute kidney injury mice

Huang

Peng

et al. 2023

Renal Failure

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Aim Renal tubular epithelial cell (RTEC) apoptosis is important in acute kidney injury (AKI). Calcium/calmodulin-dependent protein kinase II (CaMKII) plays an important role in cell apoptosis, but its potential role in AKI remains unknown. Methods Using co-immunoprecipitation, immunofluorescence, immunohistochemistry, western blotting, flow cytometry, and cell transfection, this study aimed to verify whether CaMKII is involved in RTEC apoptosis and to explore the underlying mechanism. Results We found that CaMKII was involved in RTEC apoptosis. In adriamycin-induced AKI mice, serum creatinine levels, cell apoptosis, CaMKII activity, and nuclear factor of activated T cells 2 (NFAT2) levels increased, whereas nuclear Yes-associated protein (YAP) expression decreased; inhibition of CaMKII activity reversed these changes. Phosphorylated CaMKII could bind to phosphorylated YAP in the cytoplasm and block it from entering the nucleus, thereby failing to inhibit NFAT2-mediated cell apoptosis. Sequestrated phosphorylated YAP in the RTEC cytoplasm was finally degraded by ubiquitination. Conclusion CaMKII may regulate RTEC apoptosis through YAP/NFAT2 in AKI mice. CaMKII may be a potent molecular target for AKI treatment.

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Section: Discussionmentioning

confidence: 99%

CaMKII may regulate renal tubular epithelial cell apoptosis through YAP/NFAT2 in acute kidney injury mice

Huang

Peng

et al. 2023

Renal Failure

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“…The current study demonstrates that SKI and its three components chrysophanol, emodin, and rhein inhibit tubulointerstitial fibrosis by inhibiting the RAS/Wnt/β-catenin signalling axis in adenine-induced CKD rats. Recent studies show that emodin ameliorates tubulointerstitial fibrosis ( Wang et al, 2022b ; Xu et al, 2022 ). In addition, several publications revealed that rhein improves renal fibrosis and is associated with the nuclear factor kappa B and Twist1 pathways ( Chen et al, 2022 ; Song et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway

et al. 2022

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Chronic kidney disease (CKD) is a major worldwide public health problem. The increase in the number of patients with CKD and end-stage kidney disease requesting renal dialysis or transplantation will progress to epidemic proportions in the next several decades. Although blocking the renin-angiotensin system (RAS) has been used as a first-line standard therapy in patients with hypertension and CKD, patients still progress towards end-stage kidney disease, which might be closely associated with compensatory renin expression subsequent to RAS blockade through a homeostatic mechanism. The Wnt/β-catenin signalling pathway is the master upstream regulator that controls multiple intrarenal RAS genes. As Wnt/β-catenin regulates multiple RAS genes, we inferred that this pathway might also be implicated in blood pressure control. Therefore, discovering new medications to synchronously target multiple RAS genes is necessary and essential for the effective treatment of patients with CKD. We hypothesized that Shenkang injection (SKI), which is widely used to treat CKD patients, might ameliorate CKD by inhibiting the activation of multiple RAS genes via the Wnt/β-catenin signalling pathway. To test this hypothesis, we used adenine-induced CKD rats and angiotensin II (AngII)-induced HK-2 and NRK-49F cells. Treatment with SKI inhibited renal function decline, hypertension and renal fibrosis. Mechanistically, SKI abrogated the increased protein expression of multiple RAS elements, including angiotensin-converting enzyme and angiotensin II type 1 receptor, as well as Wnt1, β-catenin and downstream target genes, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in adenine-induced rats, which was verified in AngII-induced HK-2 and NRK-49F cells. Similarly, our results further indicated that treatment with rhein isolated from SKI attenuated renal function decline and epithelial-to-mesenchymal transition and repressed RAS activation and the hyperactive Wnt/β-catenin signalling pathway in both adenine-induced rats and AngII-induced HK-2 and NRK-49F cells. This study first revealed that SKI repressed epithelial-to-mesenchymal transition by synchronously targeting multiple RAS elements by blocking the hyperactive Wnt/β-catenin signalling pathway.

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“…Meanwhile, curcumin can target FIS1 and prevent elevation of FIS1 as well as prevent decrease in mitochondrial fusion protein; the protective and preventive role of curcumin in cisplatin-induced AKI cannot be ignored [ 135 ]. Emodin is an anthraquinone derivative that significantly prevents increase in DRP1 expression and, thus, promotes reduced renal cell injury in AKI [ 154 ], and magnesium stigmasterate B plays a similar protective role in AKI by targeting DRP1 to renal cells [ 155 ]. High glucose often causes fragmentation of the mitochondrial network and cell death.…”

Section: Drugs Targeting Fis1 and Drp1 And Their Role In Kidney Diseasementioning

confidence: 99%

The role of Mitochondrial Fission Proteins in Mitochondrial Dynamics in Kidney Disease

Qin

Shi

2022

IJMS

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Mitochondria have many forms and can change their shape through fusion and fission of the outer and inner membranes, called “mitochondrial dynamics”. Mitochondrial outer membrane proteins, such as mitochondrial fission protein 1 (FIS1), mitochondrial fission factor (MFF), mitochondrial 98 dynamics proteins of 49 kDa (MiD49), and mitochondrial dynamics proteins of 51 kDa (MiD51), can aggregate at the outer mitochondrial membrane and thus attract Dynamin-related protein 1 (DRP1) from the cytoplasm to the outer mitochondrial membrane, where DRP1 can perform a scissor-like function to cut a complete mitochondrion into two separate mitochondria. Other organelles can promote mitochondrial fission alongside mitochondria. FIS1 plays an important role in mitochondrial–lysosomal contacts, differentiating itself from other mitochondrial-fission-associated proteins. The contact between the two can also induce asymmetric mitochondrial fission. The kidney is a mitochondria-rich organ, requiring large amounts of mitochondria to produce energy for blood circulation and waste elimination. Pathological increases in mitochondrial fission can lead to kidney damage that can be ameliorated by suppressing their excessive fission. This article reviews the current knowledge on the key role of mitochondrial-fission-associated proteins in the pathogenesis of kidney injury and the role of their various post-translational modifications in activation or degradation of fission-associated proteins and targeted drug therapy.

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Emodin prevents renal ischemia-reperfusion injury via suppression of CAMKII/DRP1-mediated mitochondrial fission

Cited by 34 publications

References 47 publications

CaMKII may regulate renal tubular epithelial cell apoptosis through YAP/NFAT2 in acute kidney injury mice

CaMKII may regulate renal tubular epithelial cell apoptosis through YAP/NFAT2 in acute kidney injury mice

Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway

The role of Mitochondrial Fission Proteins in Mitochondrial Dynamics in Kidney Disease

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