Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway

Lin, Yong-Song; Wu, Mai Szu; Lin, Yuh Feng; Chen, Changrong; Chen, Chang Yu; Chen, Chang Jui; Shen, Che Chou; Chen, Kuan Chou; Peng, Chiung Chi

doi:10.3390/ijms20071570

Cited by 24 publications

(27 citation statements)

References 43 publications

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“…Particularly, SREBP1-c contributes to the increased de novo synthesis of fatty acids by regulating both FAS and ACC expression [85]. Moreover, calcium channel blocker Nifedipine decreased AMPK activity and increased SREBP1/2 and intrarenal lipids [86]. These studies confirm the role of AMPK dysregulation in renal lipid accumulation via the SREBP pathway.…”

Section: Ampk and Renal Lipid Metabolismmentioning

confidence: 55%

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Critical Role for AMPK in Metabolic Disease-Induced Chronic Kidney Disease

Juszczak

Caron

Mathew

et al. 2020

IJMS

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Chronic kidney disease (CKD) is prevalent in 9.1% of the global population and is a significant public health problem associated with increased morbidity and mortality. CKD is associated with highly prevalent physiological and metabolic disturbances such as hypertension, obesity, insulin resistance, cardiovascular disease, and aging, which are also risk factors for CKD pathogenesis and progression. Podocytes and proximal tubular cells of the kidney strongly express AMP-activated protein kinase (AMPK). AMPK plays essential roles in glucose and lipid metabolism, cell survival, growth, and inflammation. Thus, metabolic disease-induced renal diseases like obesity-related and diabetic chronic kidney disease demonstrate dysregulated AMPK in the kidney. Activating AMPK ameliorates the pathological and phenotypical features of both diseases. As a metabolic sensor, AMPK regulates active tubular transport and helps renal cells to survive low energy states. AMPK also exerts a key role in mitochondrial homeostasis and is known to regulate autophagy in mammalian cells. While the nutrient-sensing role of AMPK is critical in determining the fate of renal cells, the role of AMPK in kidney autophagy and mitochondrial quality control leading to pathology in metabolic disease-related CKD is not very clear and needs further investigation. This review highlights the crucial role of AMPK in renal cell dysfunction associated with metabolic diseases and aims to expand therapeutic strategies by understanding the molecular and cellular processes underlying CKD.

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Section: Ampk and Renal Lipid Metabolismmentioning

confidence: 55%

“…CD36 was upregulated in kidney biopsies of diabetic patients [92]. Moreover, CD36 upregulation in the kidney led to the inhibition of AMPK activity and subsequent lipotoxicity [86].…”

Section: Ampk and Renal Lipid Metabolismmentioning

confidence: 99%

Critical Role for AMPK in Metabolic Disease-Induced Chronic Kidney Disease

Juszczak

Caron

Mathew

et al. 2020

IJMS

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“…C. tinctoria may also decrease lipid levels through the adipose differentiation-related protein (ADRP) [157]. Lipid accumulation may also induce ROS activation [159]. In addition, C. tinctoria reduced renal inflammation and fibrosis by inhibiting the AMPK and TGF-β/Smad signaling pathways [160].…”

Section: Plant-derived Metabolitesmentioning

confidence: 99%

Inflammation and Oxidative Stress in Chronic Kidney Disease—Potential Therapeutic Role of Minerals, Vitamins and Plant-Derived Metabolites

Rapa

Iorio

Campiglia

et al. 2019

IJMS

268

208

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Chronic kidney disease (CKD) is a debilitating pathology with various causal factors, culminating in end stage renal disease (ESRD) requiring dialysis or kidney transplantation. The progression of CKD is closely associated with systemic inflammation and oxidative stress, which are responsible for the manifestation of numerous complications such as malnutrition, atherosclerosis, coronary artery calcification, heart failure, anemia and mineral and bone disorders, as well as enhanced cardiovascular mortality. In addition to conventional therapy with anti-inflammatory and antioxidative agents, growing evidence has indicated that certain minerals, vitamins and plant-derived metabolites exhibit beneficial effects in these disturbances. In the current work, we review the anti-inflammatory and antioxidant properties of various agents which could be of potential benefit in CKD/ESRD. However, the related studies were limited due to small sample sizes and short-term follow-up in many trials. Therefore, studies of several anti-inflammatory and antioxidant agents with long-term follow-ups are necessary.

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“…The expression level of CD36 is higher in kidney with acute or chronic damage, and lipid disorders will stimulate the up-regulation of CD36. Furthermore, CD36 can promote the uptake of lipid from plasma to tissue (Hua et al 2015, Lin et al 2019, Nosadini and Tonolo 2011, Yang et al 2017. Among our results, the top 10 GO terms of non-LN module includes two terms about lipid metabolism: fatty acid catabolic process (p = 8.03e-22) and fatty acid metabolic process (p = 2.62e-20), implying that lipid disorders exist in the glomerular tissue, in which CD36 may take part.…”

Section: Discussionmentioning

confidence: 57%

“…There is probably similar pathogenesis in the progression of LN. Ectopic lipid deposition in kidney may cause lipotoxicity and further affect the function of the kidney (Lin et al 2019). CD36 is a multifunctional protein function as a key molecule in the uptake of long-chain fatty acids, which is the main component of fatty acids uptake system in the kidney and plays a critical rule in the development of CKD (Gai et al 2019).…”

Section: Discussionmentioning

confidence: 99%

Peer Review #1 of "CD36 identified by weighted gene co-expression network analysis as a hub candidate gene in lupus nephritis (v0.2)"

2019

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Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), which often progresses to end-stage renal disease (ESRD) and ultimately leads to death. At present, there are no definitive therapies towards LN, so that illuminating the molecular mechanism behind the disease has become an urgent task for researchers. Bioinformatics has become a widely utilized method for exploring genes related to disease. This study set out to conduct weighted gene co-expression network analysis (WGCNA) and screen the hub gene of LN. We performed WGCNA on the microarray expression profile dataset of GSE104948 from Gene Expression Omnibus (GEO) database with 18 normal and 21 LN samples of glomerulus. A total of 5,942 genes were divided into 5 co-expression modules, one of which was significantly correlated to LN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the LN-related module and the module was proved to be associated mainly with the activation of inflammation, immune response, cytokines, and immune cells. Genes in the most significant GO terms were extracted for sub-networks of WGNCA. We evaluated the centrality of genes in the sub-networks by Maximal Clique Centrality (MCC) method and CD36 was ultimately screened out as a hub candidate gene of the pathogenesis of LN. The result was verified by its differentially expressed level between normal and LN in GSE104948 and the other three multi-microarray datasets of GEO. Moreover, we further demonstrated that the expression level of CD36 is related to the WHO Lupus Nephritis Class of LN patients with the help of Nephroseq database. The current study proposed CD36 as a vital candidate gene in LN for the first time and CD36 may perform as a brandnew biomarker or therapeutic target of LN in the future.

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Nifedipine Modulates Renal Lipogenesis via the AMPK-SREBP Transcriptional Pathway

Cited by 24 publications

References 43 publications

Critical Role for AMPK in Metabolic Disease-Induced Chronic Kidney Disease

Critical Role for AMPK in Metabolic Disease-Induced Chronic Kidney Disease

Inflammation and Oxidative Stress in Chronic Kidney Disease—Potential Therapeutic Role of Minerals, Vitamins and Plant-Derived Metabolites

Peer Review #1 of "CD36 identified by weighted gene co-expression network analysis as a hub candidate gene in lupus nephritis (v0.2)"

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