Targeting energy pathways in kidney disease: the roles of sirtuins, AMPK, and PGC1α

Clark, Amanda J.; Parikh, Samir M.

doi:10.1016/j.kint.2020.09.037

Cited by 48 publications

(39 citation statements)

References 155 publications

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“…Recent advances in studies on novel glucose-lowering agents promote the new era in the advanced glycemic control and concurrently promise cardiorenal protection in DKD management. Figure 3 depicts the current high-profile classes of potential novel anti-hyperglycemic agents for DKD, mainly grouped into renal tubule-targeting therapies, incretin therapies, and energy pathways-targeting therapies ( 117 , 118 ). The tubule-targeting medicine, SGLT2i also affects the energy pathway associated with enhanced sirtuin1 and hypoxia-inducible factor (HIF)-2a signaling ( 119 ).…”

Section: Renal Tubule-targeting Therapeutics: a New Era For Dkd Managementmentioning

confidence: 99%

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

et al. 2021

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Over decades, substantial progress has been achieved in understanding the pathogenesis of proteinuria in diabetic kidney disease (DKD), biomarkers for DKD screening, diagnosis, and prognosis, as well as novel hypoglycemia agents in clinical trials, thereby rendering more attention focused on the role of renal tubules in DKD. Previous studies have demonstrated that morphological and functional changes in renal tubules are highly involved in the occurrence and development of DKD. Novel tubular biomarkers have shown some clinical importance. However, there are many challenges to transition into personalized diagnosis and guidance for individual therapy in clinical practice. Large-scale clinical trials suggested the clinical relevance of increased proximal reabsorption and hyperfiltration by sodium-glucose cotransporter-2 (SGLT2) to improve renal outcomes in patients with diabetes, further promoting the emergence of renal tubulocentric research. Therefore, this review summarized the recent progress in the pathophysiology associated with involved mechanisms of renal tubules, potential tubular biomarkers with clinical application, and renal tubular factors in DKD management. The mechanism of kidney protection and impressive results from clinical trials of SGLT2 inhibitors were summarized and discussed, offering a comprehensive update on therapeutic strategies targeting renal tubules.

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Section: Renal Tubule-targeting Therapeutics: a New Era For Dkd Managementmentioning

confidence: 99%

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

et al. 2021

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“…These adaptive changes may be protective, as growing evidence suggests that excessive activation of PI3K-AKT signalling can cause renal fibrosis and kidney dysfunction [ 34 ]. On the other hand, AMPK signalling inhibits cell growth and translation; therefore, reduced AMPK activation would favour renal growth [ 58 ]. AMPK controls lipid homeostasis and mitochondrial dynamics [ 59 , 60 ], and work is required to assess the relationships between reduced renal AMPK activation and the down-regulation of proteins implicated in the lipoprotein activity that we detected in the blood of pregnant mice.…”

Section: Discussionmentioning

confidence: 99%

Identification of Structural and Molecular Signatures Mediating Adaptive Changes in the Mouse Kidney in Response to Pregnancy

López-Tello

Jiménez-Martínez

Salazar‐Petres

et al. 2022

IJMS

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Pregnancy is characterized by adaptations in the function of several maternal body systems that ensure the development of the fetus whilst maintaining health of the mother. The renal system is responsible for water and electrolyte balance, as well as waste removal. Thus, it is imperative that structural and functional changes occur in the kidney during pregnancy. However, our knowledge of the precise morphological and molecular mechanisms occurring in the kidney during pregnancy is still very limited. Here, we investigated the changes occurring in the mouse kidney during pregnancy by performing an integrated analysis involving histology, gene and protein expression assays, mass spectrometry profiling and bioinformatics. Data from non-pregnant and pregnant mice were used to identify critical signalling pathways mediating changes in the maternal kidneys. We observed an expansion of renal medulla due to proliferation and infiltration of interstitial cellular constituents, as well as alterations in the activity of key cellular signalling pathways (e.g., AKT, AMPK and MAPKs) and genes involved in cell growth/metabolism (e.g., Cdc6, Foxm1 and Rb1) in the kidneys during pregnancy. We also generated plasma and urine proteomic profiles, identifying unique proteins in pregnancy. These proteins could be used to monitor and study potential mechanisms of renal adaptations during pregnancy and disease.

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“…In AKI, the pathophysiological role of peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α), a master regulator of mitochondrial biogenesis, has also been extensively investigated. Tubular PGC1α expression is suppressed in AKI, leading to impaired mitochondrial function, such as decreased mitochondrial biogenesis, β-oxidation, and ATP production [18].…”

Section: Mitochondrial Stress In Kidney Diseasementioning

confidence: 99%

Organelle Stress and Metabolic Derangement in Kidney Disease

Inagi

2022

IJMS

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Advanced multiomics analysis has revealed novel pathophysiological mechanisms in kidney disease. In particular, proteomic and metabolomic analysis shed light on mitochondrial dysfunction (mitochondrial stress) by glycation in diabetic or age-related kidney disease. Further, metabolic damage often results from organelle stress, such as mitochondrial stress and endoplasmic reticulum (ER) stress, as well as interorganelle communication, or “organelle crosstalk”, in various kidney cells. These contribute to progression of the disease phenotype. Aberrant tubular mitochondrial lipid metabolism leads to tubular inflammation and fibrosis. This review article summarizes updated evidence regarding organelle stress, organelle crosstalk, and metabolic derangement in kidney disease.

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Targeting energy pathways in kidney disease: the roles of sirtuins, AMPK, and PGC1α

Cited by 48 publications

References 155 publications

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

Current Challenges and Future Perspectives of Renal Tubular Dysfunction in Diabetic Kidney Disease

Identification of Structural and Molecular Signatures Mediating Adaptive Changes in the Mouse Kidney in Response to Pregnancy

Organelle Stress and Metabolic Derangement in Kidney Disease

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