Dataset Information

Role of SIK1 in the transition of acute kidney injury into chronic kidney disease.

ABSTRACT:

Background

Acute kidney injury (AKI), with a high morbidity and mortality, is recognized as a risk factor for chronic kidney disease (CKD). AKI-CKD transition has been regarded as one of the most pressing unmet needs in renal diseases. Recently, studies have showed that salt inducible kinase 1 (SIK1) plays a role in epithelial-mesenchymal transition (EMT) and inflammation, which are the hallmarks of AKI-CKD transition. However, whether SIK1 is involved in AKI-CKD transition and by what mechanism it regulates AKI-CKD transition remains unknown.

Methods

We firstly detected the expression of SIK1 in kidney tissues of AKI patients and AKI mice by immunohistochemistry staining, and then we established Aristolochic acid (AA)-induced AKI-CKD transition model in C57BL/6 mice and HK2 cells. Subsequently, we performed immunohistochemistry staining, ELISA, real-time PCR, Western blot, immunofluorescence staining and Transwell assay to explore the role and underlying mechanism of SIK1 on AKI-CKD transition.

Results

The expression of SIK1 was down-regulated in AKI patients, AKI mice, AA-induced AKI-CKD transition mice, and HK2 cells. Functional analysis revealed that overexpression of SIK1 alleviated AA-induced AKI-CKD transition and HK2 cells injury in vivo and in vitro. Mechanistically, we demonstrated that SIK1 mediated AA-induced AKI-CKD transition by regulating WNT/?-catenin signaling, the canonical pathway involved in EMT, inflammation and renal fibrosis. In addition, we discovered that inhibition of WNT/?-catenin pathway and its downstream transcription factor Twist1 ameliorated HK2 cells injury, delaying the progression of AKI-CKD transition.

Conclusions

Our study demonstrated, for the first time, a protective role of SIK1 in AKI-CKD transition by regulating WNT/?-catenin signaling pathway and its downstream transcription factor Twist1, which will provide novel insights into the prevention and treatment AKI-CKD transition in the future.

SUBMITTER: Hu J

PROVIDER: S-EPMC7885408 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Role of SIK1 in the transition of acute kidney injury into chronic kidney disease.

Hu Jinxiu J Qiao Jiao J Yu Qun Q Liu Bing B Zhen Junhui J Liu Yue Y Ma Qiqi Q Li Yanmei Y Wang Qianhui Q Wang Cheng C Lv Zhimei Z

Journal of translational medicine 20210215 1

<h4>Background</h4>Acute kidney injury (AKI), with a high morbidity and mortality, is recognized as a risk factor for chronic kidney disease (CKD). AKI-CKD transition has been regarded as one of the most pressing unmet needs in renal diseases. Recently, studies have showed that salt inducible kinase 1 (SIK1) plays a role in epithelial-mesenchymal transition (EMT) and inflammation, which are the hallmarks of AKI-CKD transition. However, whether SIK1 is involved in AKI-CKD transition and by what m ...[more]

PMID: 33588892

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Project description:Mitochondria are heterogeneous and highly dynamic organelles, playing critical roles in adenosine triphosphate (ATP) synthesis, metabolic modulation, reactive oxygen species (ROS) generation, and cell differentiation and death. Mitochondrial dysfunction has been recognized as a contributor in many diseases. The kidney is an organ enriched in mitochondria and with high energy demand in the human body. Recent studies have been focusing on how mitochondrial dysfunction contributes to the pathogenesis of different forms of kidney diseases, including acute kidney injury (AKI) and chronic kidney disease (CKD). AKI has been linked to an increased risk of developing CKD. AKI and CKD have a broad clinical syndrome and a substantial impact on morbidity and mortality, encompassing various etiologies and representing important challenges for global public health. Renal mitochondrial disorders are a common feature of diverse forms of AKI and CKD, which result from defects in mitochondrial structure, dynamics, and biogenesis as well as crosstalk of mitochondria with other organelles. Persistent dysregulation of mitochondrial homeostasis in AKI and CKD affects diverse cellular pathways, leading to an increase in renal microvascular loss, oxidative stress, apoptosis, and eventually renal failure. It is important to understand the cellular and molecular events that govern mitochondria functions and pathophysiology in AKI and CKD, which should facilitate the development of novel therapeutic strategies. This review provides an overview of the molecular insights of the mitochondria and the specific pathogenic mechanisms of mitochondrial dysfunction in the progression of AKI, CKD, and AKI to CKD transition. We also discuss the possible beneficial effects of mitochondrial-targeted therapeutic agents for the treatment of mitochondrial dysfunction-mediated AKI and CKD, which may translate into therapeutic options to ameliorate renal injury and delay the progression of these kidney diseases.

Dataset Information

Role of SIK1 in the transition of acute kidney injury into chronic kidney disease.

Background

Methods

Results

Conclusions

Publications

Role of SIK1 in the transition of acute kidney injury into chronic kidney disease.

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