AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice

Han, Yachun; Tang, Shiqi; Liu, Yuting; Li, Aimei; Zhan, Ming; Yang, Ming; Song, Na; Zhang, Wei; Wu, Xueqin; Peng, Canhui; Zhang, Hao; Yang, Shikun

doi:10.1038/s41419-021-04184-8

Cited by 132 publications

(84 citation statements)

References 41 publications

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“…Metformin can act on NF-κB signaling, inhibit monocyte to macrophage differentiation, and suppress several pro-inflammatory cytokines in the plasma of non-diabetic patients ( Isoda et al., 2006 ). Furthermore, metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in DKD mice by activating mitophagy through Pink1 (PTEN-induced putative kinase 1) and Parkin ( Han et al., 2021 ).…”

Section: Dkd Therapy Targeting Oxidative Stress and Mitochondrial Fun...mentioning

confidence: 99%

Mitochondria-targeted drugs for diabetic kidney disease

Mima

2022

Heliyon

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Diabetic kidney disease (DKD) is one of the most frequent causes of chronic kidney disease (CKD) in the United States. Chronic hyperglycemic conditions are thought to be the primary cause of DKD. However, it is clinically difficult to achieve glycemic control in individuals with diabetes. Recent advances in mitochondrial biology have provided a new understanding of mitochondrial dysfunction in DKD. Studies have revealed impaired mitochondrial function in a variety of diabetic complications, including DKD; moreover, abnormal mitochondrial fission may be involved in the progression of DKD. It has been reported that metformin or sodium-glucose cotransporter 2 (SGLT2) inhibitors may provide renal protection by improving mitochondrial dynamics and reducing oxidative stress. Thus, drugs that target the restoration of mitochondrial function may become novel therapeutic agents for DKD. Imeglimin is the first in a new class of oral antidiabetic drugs that can reduce reactive oxygen species production and increase mitochondrial DNA synthesis. This review outlines the potential therapeutic interventions that affect mitochondrial function and prevent DKD.

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Section: Dkd Therapy Targeting Oxidative Stress and Mitochondrial Fun...mentioning

confidence: 99%

Mitochondria-targeted drugs for diabetic kidney disease

Mima

2022

Heliyon

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“…It has been shown that treatment with metformin, as an AMPK agonist, can well moderate mitophagia in epithelial cells of the proximal tubule of the kidney (Zhao and Sun 2020 ). In addition, Ya-chun Han et al Also showed that the use of metformin could decrease the risk of fibrosis in the renal interstitial tube associated with mitophage activation via the AMPK-Pink1-Parkin pathway (Han et al 2021 ). Another study showed that the use of metformin in renal nephrectomy models following renal disease could halt the progression of chronic renal disease, including renal fibrosis, and that activation of AMPK may contribute to the protective effect of metformin nephroprotechnics (Borges et al 2020 ).…”

Section: Metformin and Therapeutic Goalsmentioning

confidence: 99%

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

Hasanvand

2022

Inflammopharmacol

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Metformin can suppress gluconeogenesis and reduce blood sugar by activating adenosine monophosphate-activated protein kinase (AMPK) and inducing small heterodimer partner (SHP) expression in the liver cells. The main mechanism of metformin’s action is related to its activation of the AMPK enzyme and regulation of the energy balance. AMPK is a heterothermic serine/threonine kinase made of a catalytic alpha subunit and two subunits of beta and a gamma regulator. This enzyme can measure the intracellular ratio of AMP/ATP. If this ratio is high, the amino acid threonine 172 available in its alpha chain would be activated by the phosphorylated liver kinase B1 (LKB1), leading to AMPK activation. Several studies have indicated that apart from its significant role in the reduction of blood glucose level, metformin activates the AMPK enzyme that in turn has various efficient impacts on the regulation of various processes, including controlling inflammatory conditions, altering the differentiation pathway of immune and non-immune cell pathways, and the amelioration of various cancers, liver diseases, inflammatory bowel disease (IBD), kidney diseases, neurological disorders, etc. Metformin’s activation of AMPK enables it to control inflammatory conditions, improve oxidative status, regulate the differentiation pathways of various cells, change the pathological process in various diseases, and finally have positive therapeutic effects on them. Due to the activation of AMPK and its role in regulating several subcellular signalling pathways, metformin can be effective in altering the cells’ proliferation and differentiation pathways and eventually in the prevention and treatment of certain diseases. Graphical abstract

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“…As known, mitochondria mainly provide ATP and energy to maintain cellular homeostasis and regulate the communication between cells and tissues. Recent studies showed that mitochondria play an important role in HFD-induced renal inflammatory injury ( Sun et al, 2020 ; Han et al, 2021 ; Lubojemska et al, 2021 ). Mitochondrial dysfunction-induced by HFD is related to mitochondrial fatty acid oxidative (FAO) impairment, dynamic change (e.g., mitochondrial fission and fusion) and mitophagy deficiency.…”

Section: Hfd-induced Renal Tubular Inflammatory Injury and Its Potential Underlying Mechanismsmentioning

confidence: 99%

“…For the molecular mechanisms involved in this progress, Unc-51-like autophagy activating kinase 1 (ULK1) has been confirmed to be inactivated in HFD-induced renal injury ( Declèves et al, 2011 , 2014 ; Sohn et al, 2017 ; Luo et al, 2019 ). More important, the recovery of mitophagy deficiency can attenuate HFD-induced renal tubular inflammatory injury ( Han et al, 2021 ). In addition, mitochondrial dynamic changes were also reported in HFD ( Chen et al, 2018 ; Sun et al, 2020 ).…”

Section: Hfd-induced Renal Tubular Inflammatory Injury and Its Potential Underlying Mechanismsmentioning

confidence: 99%

High-Fat Diet-Induced Renal Proximal Tubular Inflammatory Injury: Emerging Risk Factor of Chronic Kidney Disease

Chen

Guo

et al. 2021

Front. Physiol.

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Nowadays, with the improvements in living standards and changes in living habits, high-fat diet (HFD) has become much more common in the populations worldwide. Recent studies have shown that HFD could induce lipid accumulation, and structural and functional abnormalities, accompanied by the release of large amounts of pro-inflammatory cytokines, in proximal tubular epithelial cells (PTECs). These findings indicate that, as an emerging risk factor, PTEC injury-induced by HFD may be closely related to inflammation; however, the potential mechanisms underlying this phenomenon is still not well-known, but may involve the several inflammatory pathways, including oxidative stress-related signaling pathways, mitochondrial dysfunction, the myeloid differentiation factor 2/Toll like receptor 4 (MD2/TLR4) signaling pathway, the ERK1/2-kidney injury molecule 1 (KIM-1)-related pathway, and nuclear factor-κB (NF-κB) activation, etc., and the detailed molecular mechanisms underlying these pathways still need further investigated in the future. Based on lipid abnormalities-induced inflammation is closely related to the development and progression of chronic kidney disease (CKD), to summarize the potential mechanisms underlying HFD-induced renal proximal tubular inflammatory injury, may provide novel approaches for CKD treatment.

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AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice

Cited by 132 publications

References 41 publications

Mitochondria-targeted drugs for diabetic kidney disease

Mitochondria-targeted drugs for diabetic kidney disease

The role of AMPK-dependent pathways in cellular and molecular mechanisms of metformin: a new perspective for treatment and prevention of diseases

High-Fat Diet-Induced Renal Proximal Tubular Inflammatory Injury: Emerging Risk Factor of Chronic Kidney Disease

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