AICAR, an AMPK activator, protects against cisplatin-induced acute kidney injury through the JAK/STAT/SOCS pathway

Tsogbadrakh, Bodokhsuren; Ryu, Hyunjin; Ju, Kyung Don; Lee, Jinho; Yun, Sohyun; Yu, Kyung‐Sang; Kim, Hyo Jin; Ahn, Curie; Oh, Kook Hwan

doi:10.1016/j.bbrc.2018.12.159

Cited by 41 publications

(24 citation statements)

References 33 publications

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“…2016; Tsogbadrakh et al . 2019) so we chose a dose that was well tolerated by the pregnant dams in our study. AICAR was chosen as the AMPK agonist as its mechanism is known and it is an effective AMPK activator in vivo ; namely, AICAR is phosphorylated by adenosine kinase and converted into ZMP, an AMP mimetic, thus directly activating AMPK (Kim et al .…”

Section: Methodsmentioning

confidence: 99%

AMP‐activated protein kinase activator AICAR attenuates hypoxia‐induced murine fetal growth restriction in part by improving uterine artery blood flow

Lane

Houck

Doyle

et al. 2020

The Journal of Physiology

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Key points Pregnancy at high altitude is associated with a greater incidence of fetal growth restriction due, in part, to lesser uterine artery blood flow. AMP‐activated protein kinase (AMPK) activation vasodilates arteries and may increase uterine artery blood flow. In this study, pharmacological activation of AMPK by the drug AICAR improved fetal growth and elevated uterine artery blood flow. These results suggest that AMPK activation is a potential strategy for improving fetal growth and raising uterine artery blood flow in pregnancy, which may be important in pregnancy disorders characterized by uteroplacental ischaemia and/or fetal hypoxia. Abstract Uteroplacental hypoxia is associated with pregnancy disorders such as intrauterine growth restriction and preeclampsia, which are characterized by uteroplacental ischaemia and/or fetal hypoxia. Activation of AMP‐activated protein kinase (AMPK) results in vasodilatation and is therefore a potential therapeutic strategy for restoring uteroplacental perfusion in pregnancy disorders. In this study, C57Bl/6 mice were treated with subcutaneous pellets containing vehicle, the AMPK activator AICAR (200 mg kg−1 day−1), or the AMPK inhibitor Compound C (20 mg kg−1 day−1) beginning on gestational day 13.5, and were exposed to hypoxia starting on gestational day 14.5 that induced intrauterine growth restriction. Pharmacological AMPK activation by AICAR partially prevented hypoxia‐induced fetal growth restriction (P < 0.01), due in part to increased uterine artery blood flow (P < 0.0001). The proportion of total cardiac output flowing through the uterine artery was increased with AICAR in hypoxic mice (P < 0.001), suggesting that the vasodilator effect of AICAR was selective for the uterine circulation. Further, pharmacological inhibition of AMPK with Compound C reduced uterine artery diameter and increased uterine artery contractility in normoxic mice, providing evidence that physiological levels of AMPK activation are necessary for vasodilatation in healthy pregnancy. Two‐way ANOVA analyses indicated that hypoxia reduced AMPK activation in the uterine artery and placenta, and AICAR increased AMPK activation in these tissues compared to vehicle. These findings provide support for further investigation into the utility of pharmacological AMPK activation for treatment of fetal growth restriction.

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Section: Methodsmentioning

confidence: 99%

AMP‐activated protein kinase activator AICAR attenuates hypoxia‐induced murine fetal growth restriction in part by improving uterine artery blood flow

Lane

Houck

Doyle

et al. 2020

The Journal of Physiology

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“…Induction of Jak2/STAT3/SOCS1 pathway had a protective effect in acute kidney graft rejection [119]. In a murine model of cisplatin-induced AKI, SOCS1 expression was decreased, whereas induction of Jak2/STAT1 pathway with an AMPK activator restored SOCS1 levels and promoted renal protection [120]. Additionally, SOCS1-targeted therapy limited progression of diabetic nephropathy [121][122][123].…”

Section: Bcl3mentioning

confidence: 99%

Toll-Like Receptors in Acute Kidney Injury

Vázquez‐Carballo

Guerrero‐Hue

García‐Caballero

et al. 2021

IJMS

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Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.

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“…This study is the first to report that the JAK-STAT signaling pathway is active during the progression of HSPN. Previously, the JAK/STAT pathway has been shown to play an important role in the development of obstructive nephropathy [24], diabetic nephropathy [25], and acute kidney injury [26]. Another pathway identified in this study, the Wnt signaling pathway, has been noted to regulate many biological processes, including proliferation, migration, invasion, and apoptosis [27].…”

mentioning

confidence: 61%

An Integrated Transcriptomic and Proteomic Analysis Identifies Significant Novel Pathways for Henoch-Schönlein Purpura Nephritis Progression

Xie

Zhang

et al. 2020

BioMed Research International

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Background. Although Henoch-Schönlein purpura nephritis (HSPN) is characterized by glomerular deposition of aberrantly glycosylated immunoglobulin A1 (IgA1), the underlying mechanism of HSPN progression has not yet been completely elucidated. In this study, we integrated transcriptomic and proteomic analyses to explore the underlying mechanism of HSPN progression. Methods. RNA sequencing and tandem mass tag- (TMT-) based quantitative proteomics were used to gain serum transcriptomic and proteomic profiles of patients with different types of HSPN (3×type 1, 3×type 2, and 3×type 3). Student’s t-tests were performed to obtain the significance of the differential gene expression. The clusterProfiler package was used to conduct the functional annotation of the DEGs for both Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Results. A total of 2315 mRNAs and 30 proteins were differentially expressed between the different types of HSPN. 58 mRNAs and one protein changed continuously during HSPN development and are potential biomarkers for HSPN progression. The validation cohort (another 9 patients) confirmed the high-throughput results of the transcriptomic and proteomic analyses. A total of 385 significant pathways were related to HSPN progression, and four of them were closely related to clinical biochemical indicators and may play an important role in the progression of HSPN. Those pathways reveal that HSPN progression may be related to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury. Conclusions. Four pathways were found to be closely related to HSPN progression, and it seems that HSPN progression is mainly due to the inhibition of inflammation, promotion of apoptosis, and repair of renal injury.

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AICAR, an AMPK activator, protects against cisplatin-induced acute kidney injury through the JAK/STAT/SOCS pathway

Cited by 41 publications

References 33 publications

AMP‐activated protein kinase activator AICAR attenuates hypoxia‐induced murine fetal growth restriction in part by improving uterine artery blood flow

AMP‐activated protein kinase activator AICAR attenuates hypoxia‐induced murine fetal growth restriction in part by improving uterine artery blood flow

Toll-Like Receptors in Acute Kidney Injury

An Integrated Transcriptomic and Proteomic Analysis Identifies Significant Novel Pathways for Henoch-Schönlein Purpura Nephritis Progression

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