scholarly journals Metabolic Reprogramming in Kidney Diseases: Evidence and Therapeutic Opportunities

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Yin Li ◽  
Zixin Sha ◽  
Hui Peng
Keyword(s):  
Energy Consumption ◽  
Cancer Cells ◽  
Environmental Conditions ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Metabolic Reprogramming ◽  
Renal Cells ◽  
Prominent Feature ◽  
Important Contributor

Metabolic reprogramming originally referred to the ability of cancer cells to metabolically adapt to changes in environmental conditions to meet both energy consumption and proliferation requirements. According to recent studies, renal cells are also capable of reprogramming their metabolism after kidney injury, and these cells undergo different kinds of metabolic reprogramming in different kidney diseases. Metabolic reprogramming also plays a role in the progression and prognosis of kidney diseases. Therefore, metabolic reprogramming is not only a prominent feature but also an important contributor to the pathophysiology of kidney diseases. Here, we briefly review kidney diseases and metabolic reprogramming and discuss new ways to treat kidney diseases.

scholarly journals Interleukin-22 mediated renal metabolic reprogramming via PFKFB3 to treat kidney injury

2020 ◽  
Author(s):  
Wei Chen ◽  
Yilan Shen ◽  
Jiajun Fan ◽  
Xian Zeng ◽  
Xuyao Zhang ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Kidney Damage ◽  
Metabolic Reprogramming ◽  
Protective Effects ◽  
Interleukin 22 ◽  
Renal Tubular ◽  
Stage Renal Disease ◽  
End Stage

AbstractKidney damage initiates the deteriorating metabolic states in tubule cells that lead to the development of end-stage renal disease (ESTD). Interleukin 22 (IL-22) is an effective therapeutic antidote for kidney injury via promoting kidney recovery, but little is known about the underlying molecular mechanisms. Here we first provide evidence that IL-22 attenuates kidney injury via metabolic reprogramming of renal tubular epithelial cells (TECs). Specifically, our data suggest that IL-22 regulates mitochondrial function and glycolysis in damaged TECs. Further observations indicate that IL-22 alleviates the accumulation of mitochondrial reactive oxygen species (ROS) and dysfunctional mitochondria via the induction of AMPK/AKT signaling and PFBFK3 activities. In mice, amelioration of kidney injury and necrosis and improvement of kidney functions via regulation of these metabolism relevant signaling and mitochondrial fitness of recombinant IL-22 are certificated in cisplatin induced kidney damage and diabetic nephropathy (DN) animal models. Taken together, our findings unravel new mechanistic insights into protective effects of IL-22 on kidney and highlight the therapeutic opportunities of IL-22 and the involved metabolic regulators in various kidney diseases.

The Engaged Role of Tumor Microenvironment in Cancer Metabolism: Focusing on Cancer-Associated Fibroblast and Exosome Mediators

2020 ◽  
Vol 21 (2) ◽  
pp. 254-266 ◽  
Author(s):  
Khandan Ilkhani ◽  
Milad Bastami ◽  
Soheila Delgir ◽  
Asma Safi ◽  
Shahrzad Talebian ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cancer Metabolism ◽  
Krebs Cycle ◽  
Metabolic Reprogramming ◽  
Cancer Management ◽  
Cancer Associated Fibroblast ◽  
Potential Biomarker ◽  
Close Relationship ◽  
Microenvironmental Factors

: Metabolic reprogramming is a significant property of various cancer cells, which most commonly arises from the Tumor Microenvironment (TME). The events of metabolic pathways include the Warburg effect, shifting in Krebs cycle metabolites, and the rate of oxidative phosphorylation, potentially providing energy and structural requirements for the development and invasiveness of cancer cells. TME and tumor metabolism shifting have a close relationship through bidirectional signaling pathways between stromal and tumor cells. Cancer- Associated Fibroblasts (CAFs), as the most dominant cells of TME, play a crucial role in the aberrant metabolism of cancer. Furthermore, the stated relationship can affect survival, progression, and metastasis in cancer development. Recently, exosomes are considered one of the most prominent factors in cellular communications considering effective content and bidirectional mediatory effect between tumor and stromal cells. In this regard, CAF-Derived Exosomes (CDE) exhibit an efficient obligation to induce metabolic reprogramming for promoting growth and metastasis of cancer cells. The understanding of cancer metabolism, including factors related to TME, could lead to the discovery of a potential biomarker for diagnostic and therapeutic approaches in cancer management. This review focuses on the association between metabolic reprogramming and engaged microenvironmental, factors such as CAFs, and the associated derived exosomes.

Metabolic reprogramming for cancer cells and their microenvironment: Beyond the Warburg Effect

2018 ◽  
Vol 1870 (1) ◽  
pp. 51-66 ◽  
Author(s):  
Linchong Sun ◽  
Caixia Suo ◽  
Shi-ting Li ◽  
Huafeng Zhang ◽  
Ping Gao
Keyword(s):  
Cancer Cells ◽  
Warburg Effect ◽  
Metabolic Reprogramming ◽  
The Warburg Effect

scholarly journals Nephrotoxicity of Herbal Products in Europe—A Review of an Underestimated Problem of Nephrotoxicity of Herbal Products

2021 ◽  
Vol 22 (8) ◽  
pp. 4132
Author(s):  
Katarzyna Kiliś-Pstrusińska ◽  
Anna Wiela-Hojeńska
Keyword(s):  
Kidney Diseases ◽  
Herbal Medicines ◽  
Kidney Injury ◽  
Herbal Products ◽  
Chronic Kidney Diseases ◽  
European Origin ◽  
Synthetic Drugs ◽  
The Many ◽  
Pharmacologically Active ◽  
Traditional Chinese Herbal Medicines

Currently in Europe, despite the many advances in production technology of synthetic drugs, the interest in natural herbal medicines continues to increase. One of the reasons for their popular use is the assumption that natural equals safe. However, herbal medicines contain pharmacologically active ingredients, some of which have been associated with adverse effects. Kidneys are particularly susceptible to injury induced by toxins, including poisonous constituents from medicinal plants. The most recognized herb-induced kidney injury is aristolochic acid nephropathy connected with misuse of certain Traditional Chinese herbal medicines. Data concerning nephrotoxicity of plant species of European origin are scarce. Here, we critically review significant data of the nephrotoxicity of several plants used in European phytotherapy, including Artemisia herba-alba, Glycyrrhiza glabra, Euphorbia paralias, and Aloe). Causative mechanisms and factors predisposing to intoxications from the use of herbs are discussed. The basic intention of this review is to improve pharmacovigilance of herbal medicine, especially in patients with chronic kidney diseases.

scholarly journals Matrix Stiffness Modulates Metabolic Interaction between Human Stromal and Breast Cancer Cells to Stimulate Epithelial Motility

Metabolites ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 432
Author(s):  
Iván Ponce ◽  
Nelson Garrido ◽  
Nicolás Tobar ◽  
Francisco Melo ◽  
Patricio C. Smith ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Stromal Cells ◽  
Glucose Transporter ◽  
Lactate Production ◽  
Resonance Energy ◽  
Metabolic Reprogramming ◽  
Dependent Manner ◽  
Functional Link

Breast tumors belong to the type of desmoplastic lesion in which a stiffer tissue structure is a determinant of breast cancer progression and constitutes a risk factor for breast cancer development. It has been proposed that cancer-associated stromal cells (responsible for this fibrotic phenomenon) are able to metabolize glucose via lactate production, which supports the catabolic metabolism of cancer cells. The aim of this work was to investigate the possible functional link between these two processes. To measure the effect of matrix rigidity on metabolic determinations, we used compliant elastic polyacrylamide gels as a substrate material, to which matrix molecules were covalently linked. We evaluated metabolite transport in stromal cells using two different FRET (Fluorescence Resonance Energy Transfer) nanosensors specific for glucose and lactate. Cell migration/invasion was evaluated using Transwell devices. We show that increased stiffness stimulates lactate production and glucose uptake by mammary fibroblasts. This response was correlated with the expression of stromal glucose transporter Glut1 and monocarboxylate transporters MCT4. Moreover, mammary stromal cells cultured on stiff matrices generated soluble factors that stimulated epithelial breast migration in a stiffness-dependent manner. Using a normal breast stromal cell line, we found that a stiffer extracellular matrix favors the acquisition mechanistical properties that promote metabolic reprograming and also constitute a stimulus for epithelial motility. This new knowledge will help us to better understand the complex relationship between fibrosis, metabolic reprogramming, and cancer malignancy.

scholarly journals Current Trends in Non-Invasive Imaging of Interactions in the Liver Tumor Microenvironment Mediated by Tumor Metabolism

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3645
Author(s):  
Isabel Theresa Schobert ◽  
Lynn Jeanette Savic
Keyword(s):  
Tumor Microenvironment ◽  
Liver Cancer ◽  
Cancer Cells ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Tumor Metabolism ◽  
Resistance Mechanisms ◽  
Metabolic Reprogramming ◽  
Non Invasive

With the increasing understanding of resistance mechanisms mediated by the metabolic reprogramming in cancer cells, there is a growing clinical interest in imaging technologies that allow for the non-invasive characterization of tumor metabolism and the interactions of cancer cells with the tumor microenvironment (TME) mediated through tumor metabolism. Specifically, tumor glycolysis and subsequent tissue acidosis in the realms of the Warburg effect may promote an immunosuppressive TME, causing a substantial barrier to the clinical efficacy of numerous immuno-oncologic treatments. Thus, imaging the varying individual compositions of the TME may provide a more accurate characterization of the individual tumor. This approach can help to identify the most suitable therapy for each individual patient and design new targeted treatment strategies that disable resistance mechanisms in liver cancer. This review article focuses on non-invasive positron-emission tomography (PET)- and MR-based imaging techniques that aim to visualize the crosstalk between tumor cells and their microenvironment in liver cancer mediated by tumor metabolism.

scholarly journals Phytochemicals Block Glucose Utilization and Lipid Synthesis to Counteract Metabolic Reprogramming in Cancer Cells

2021 ◽  
Vol 11 (3) ◽  
pp. 1259
Author(s):  
Qiong Wu ◽  
Bo Zhao ◽  
Guangchao Sui ◽  
Jinming Shi
Keyword(s):  
Cancer Cells ◽  
Metabolic Pathways ◽  
De Novo ◽  
Aerobic Glycolysis ◽  
Structural Characteristics ◽  
Natural Compounds ◽  
Metabolic Reprogramming ◽  
De Novo Lipogenesis ◽  
Anticancer Activities ◽  
Substrate Analogs

Aberrant metabolism is one of the hallmarks of cancers. The contributions of dysregulated metabolism to cancer development, such as tumor cell survival, metastasis and drug resistance, have been extensively characterized. “Reprogrammed” metabolic pathways in cancer cells are mainly represented by excessive glucose consumption and hyperactive de novo lipogenesis. Natural compounds with anticancer activities are constantly being demonstrated to target metabolic processes, such as glucose transport, aerobic glycolysis, fatty acid synthesis and desaturation. However, their molecular targets and underlying anticancer mechanisms remain largely unclear or controversial. Mounting evidence indicated that these natural compounds could modulate the expression of key regulatory enzymes in various metabolic pathways at transcriptional and translational levels. Meanwhile, natural compounds could also inhibit the activities of these enzymes by acting as substrate analogs or altering their protein conformations. The actions of natural compounds in the crosstalk between metabolism modulation and cancer cell destiny have become increasingly attractive. In this review, we summarize the activities of natural small molecules in inhibiting key enzymes of metabolic pathways. We illustrate the structural characteristics of these compounds at the molecular level as either inhibitor of various enzymes or regulators of metabolic pathways in cancer cells. Our ultimate goal is to both facilitate the clinical application of natural compounds in cancer therapies and promote the development of novel anticancer therapeutics.

scholarly journals CD73 Overexpression in Podocytes: A Novel Marker of Podocyte Injury in Human Kidney Disease

2021 ◽  
Vol 22 (14) ◽  
pp. 7642
Author(s):  
Zoran V. Popovic ◽  
Felix Bestvater ◽  
Damir Krunic ◽  
Bernhard K. Krämer ◽  
Raoul Bergner ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Membranous Glomerulonephritis ◽  
Human Kidney ◽  
Protective Role ◽  
Control Group ◽  
Podocyte Injury ◽  
Ccr2 Expression ◽  
Cd73 Expression

The CD73 pathway is an important anti-inflammatory mechanism in various disease settings. Observations in mouse models suggested that CD73 might have a protective role in kidney damage; however, no direct evidence of its role in human kidney disease has been described to date. Here, we hypothesized that podocyte injury in human kidney diseases alters CD73 expression that may facilitate the diagnosis of podocytopathies. We assessed the expression of CD73 and one of its functionally important targets, the C-C chemokine receptor type 2 (CCR2), in podocytes from kidney biopsies of 39 patients with podocytopathy (including focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), membranous glomerulonephritis (MGN) and amyloidosis) and a control group. Podocyte CD73 expression in each of the disease groups was significantly increased in comparison to controls (p < 0.001–p < 0.0001). Moreover, there was a marked negative correlation between CD73 and CCR2 expression, as confirmed by immunohistochemistry and immunofluorescence (Pearson r = −0.5068, p = 0.0031; Pearson r = −0.4705, p = 0.0313, respectively), thus suggesting a protective role of CD73 in kidney injury. Finally, we identify CD73 as a novel potential diagnostic marker of human podocytopathies, particularly of MCD that has been notorious for the lack of pathological features recognizable by light microscopy and immunohistochemistry.

scholarly journals Granulomatous interstitial nephritis in a patient with SARS-CoV-2 infection

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Katarzyna Szajek ◽  
Marie-Elisabeth Kajdi ◽  
Valerie A. Luyckx ◽  
Thomas Hans Fehr ◽  
Ariana Gaspert ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Interstitial Nephritis ◽  
Kidney Biopsy ◽  
Kidney Diseases ◽  
Case Reports ◽  
Kidney Injury ◽  
Maculopapular Rash ◽  
Tubular Injury ◽  
Granulomatous Interstitial Nephritis ◽  
First Case

Abstract Background Acute kidney injury (AKI) associated with severe coronavirus disease 19 (COVID-19) is common and is a significant predictor of morbidity and mortality, especially when dialysis is required. Case reports and autopsy series have revealed that most patients with COVID-19 – associated acute kidney injury have evidence of acute tubular injury and necrosis - not unexpected in critically ill patients. Others have been found to have collapsing glomerulopathy, thrombotic microangiopathy and diverse underlying kidney diseases. A primary kidney pathology related to COVID-19 has not yet emerged. Thus far direct infection of the kidney, or its impact on clinical disease remains controversial. The management of AKI is currently supportive. Case Presentation The patient presented here was positive for SARS-CoV-2, had severe acute respiratory distress syndrome and multi-organ failure. Within days of admission to the intensive care unit he developed oliguric acute kidney failure requiring dialysis. Acute kidney injury developed in the setting of hemodynamic instability, sepsis and a maculopapular rash. Over the ensuing days the patient also developed transfusion-requiring severe hemolysis which was Coombs negative. Schistocytes were present on the peripheral smear. Given the broad differential diagnoses for acute kidney injury, a kidney biopsy was performed and revealed granulomatous tubulo-interstitial nephritis with some acute tubular injury. Based on the biopsy findings, a decision was taken to adjust medications and initiate corticosteroids for presumed medication-induced interstitial nephritis, hemolysis and maculo-papular rash. The kidney function and hemolysis improved over the subsequent days and the patient was discharged to a rehabilitation facility, no-longer required dialysis. Conclusions Acute kidney injury in patients with severe COVID-19 may have multiple causes. We present the first case of granulomatous interstitial nephritis in a patient with COVID-19. Drug-reactions may be more frequent than currently recognized in COVID-19 and are potentially reversible. The kidney biopsy findings in this case led to a change in therapy, which was associated with subsequent patient improvement. Kidney biopsy may therefore have significant value in pulling together a clinical diagnosis, and may impact outcome if a treatable cause is identified.

scholarly journals Protein Acetylation at the Interface of Genetics, Epigenetics and Environment in Cancer

Metabolites ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 216
Author(s):  
Mio Harachi ◽  
Kenta Masui ◽  
Webster K. Cavenee ◽  
Paul S. Mischel ◽  
Noriyuki Shibata
Keyword(s):  
Cancer Cells ◽  
Intracellular Signaling ◽  
Cancer Biology ◽  
High Resolution Mass Spectrometry ◽  
Metabolic Reprogramming ◽  
Protein Acetylation ◽  
Protein Activity ◽  
Oncogenic Signaling ◽  
Intermediary Metabolites ◽  
Novel Therapeutic Strategies

Metabolic reprogramming is an emerging hallmark of cancer and is driven by abnormalities of oncogenes and tumor suppressors. Accelerated metabolism causes cancer cell aggression through the dysregulation of rate-limiting metabolic enzymes as well as by facilitating the production of intermediary metabolites. However, the mechanisms by which a shift in the metabolic landscape reshapes the intracellular signaling to promote the survival of cancer cells remain to be clarified. Recent high-resolution mass spectrometry-based proteomic analyses have spotlighted that, unexpectedly, lysine residues of numerous cytosolic as well as nuclear proteins are acetylated and that this modification modulates protein activity, sublocalization and stability, with profound impact on cellular function. More importantly, cancer cells exploit acetylation as a post-translational protein for microenvironmental adaptation, nominating it as a means for dynamic modulation of the phenotypes of cancer cells at the interface between genetics and environments. The objectives of this review were to describe the functional implications of protein lysine acetylation in cancer biology by examining recent evidence that implicates oncogenic signaling as a strong driver of protein acetylation, which might be exploitable for novel therapeutic strategies against cancer.

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