scholarly journals Autophagy in Chronic Kidney Diseases

Cells ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 61 ◽  
Author(s):  
Tien-An Lin ◽  
Victor Chien-Chia Wu ◽  
Chao-Yung Wang
Keyword(s):  
Kidney Diseases ◽  
Kidney Injury ◽  
Current Evidence ◽  
Polycystic Kidney ◽  
Recycling Process ◽  
Chronic Kidney Diseases ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Cellular Regeneration ◽  
Molecular Aspects

Autophagy is a cellular recycling process involving self-degradation and reconstruction of damaged organelles and proteins. Current evidence suggests that autophagy is critical in kidney physiology and homeostasis. In clinical studies, autophagy activations and inhibitions are linked to acute kidney injuries, chronic kidney diseases, diabetic nephropathies, and polycystic kidney diseases. Oxidative stress, inflammation, and mitochondrial dysfunction, which are implicated as important mechanisms underlying many kidney diseases, modulate the autophagy activation and inhibition and lead to cellular recycling dysfunction. Abnormal autophagy function can induce loss of podocytes, damage proximal tubular cells, and glomerulosclerosis. After acute kidney injuries, activated autophagy protects tubular cells from apoptosis and enhances cellular regeneration. Patients with chronic kidney diseases have impaired autophagy that cannot be reversed by hemodialysis. Multiple nephrotoxic medications also alter the autophagy signaling, by which the mechanistic insights of the drugs are revealed, thus providing the unique opportunity to manage the nephrotoxicity of these drugs. In this review, we summarize the current concepts of autophagy and its molecular aspects in different kidney cells pathophysiology. We also discuss the current evidence of autophagy in acute kidney injury, chronic kidney disease, toxic effects of drugs, and aging kidneys. In addition, we examine therapeutic possibilities targeting the autophagy system in kidney diseases.

scholarly journals CO-Releasing Molecule-2 Prevents Acute Kidney Injury through Suppression of ROS-Fyn-ER Stress Signaling in Mouse Model

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Md Jamal Uddin ◽  
Jeewon Jeong ◽  
Eun Seon Pak ◽  
Hunjoo Ha
Keyword(s):  
Oxidative Stress ◽  
Acute Kidney Injury ◽  
Er Stress ◽  
Stress Responses ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Oxygen Species ◽  
Chronic Kidney Diseases ◽  
Tubular Cells ◽  
Cellular Apoptosis

Acute kidney injury (AKI) most commonly appears in critically ill patients in hospitals. AKI is characterized as a quick deterioration of kidney function and has recently been identified to be tightly interlinked with chronic kidney diseases. The emerging major mediators of AKI include oxidative stress and endoplasmic reticulum (ER) stress. Carbon monoxide (CO) attenuates oxidative stress and ER stress in various cells, while Fyn, a member of the Src kinase family, is activated by oxidative stress and contributes to ER stress in skeletal muscle. Considering these, the objective of the current research was to determine (i) the involvement of Fyn in ER stress-mediated AKI and (ii) the effect of CO-releasing molecule-2 (CORM2) on reactive oxygen species- (ROS-) Fyn-ER stress-mediated AKI. Pretreatment with CORM2 (30 mg/kg) efficiently inhibited LPS (30 mg/kg)-induced oxidative stress, inflammation, and cellular apoptosis during AKI in C57BL/6J mice. Also, CORM2 efficiently suppressed the activation of Fyn and ER stress in AKI mice. Consistently, pretreatment with CORM2 inhibited oxidative stress, Fyn activation, ER stress, inflammation, and apoptosis in LPS- or H2O2-stimulated proximal epithelial tubular cells. Fyn inhibition using siRNA or an inhibitor (PP2) significantly attenuated ER stress responses in the cells. These data suggest that CORM2 may become a potential treatment option against ROS-Fyn-ER stress-mediated AKI.

scholarly journals Expression of Acsm2, a kidney-specific gene, parallels the function and maturation of proximal tubular cells

2020 ◽  
Vol 319 (4) ◽  
pp. F603-F611
Author(s):  
Hirofumi Watanabe ◽  
Robert L. Paxton ◽  
Matthew R. Tolerico ◽  
Vidya K. Nagalakshmi ◽  
Shinji Tanaka ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Kidney Development ◽  
Kidney Diseases ◽  
Kidney Injury ◽  
Specific Gene ◽  
Proximal Tubular Cells ◽  
Newborn Mice ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
High Level

The acyl-CoA synthetase medium-chain family member 2 ( Acsm2) gene was first identified and cloned by our group as a kidney-specific “ KS” gene. However, its expression pattern and function remain to be clarified. In the present study, we found that the Acsm2 gene was expressed specifically and at a high level in normal adult kidneys. Expression of Acsm2 in kidneys followed a maturational pattern: it was low in newborn mice and increased with kidney development and maturation. In situ hybridization and immunohistochemistry revealed that Acsm2 was expressed specifically in proximal tubular cells of adult kidneys. Data from the Encyclopedia of DNA Elements database revealed that the Acsm2 gene locus in the mouse has specific histone modifications related to the active transcription of the gene exclusively in kidney cells. Following acute kidney injury, partial unilateral ureteral obstruction, and chronic kidney diseases, expression of Acsm2 in the proximal tubules was significantly decreased. In human samples, the expression pattern of ACSM2A, a homolog of mouse Acsm2, was similar to that in mice, and its expression decreased with several types of renal injuries. These results indicate that the expression of Acsm2 parallels the structural and functional maturation of proximal tubular cells. Downregulation of its expression in several models of kidney disease suggests that Acms2 may serve as a novel marker of proximal tubular injury and/or dysfunction.

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 Nephrotoxicity Of Polymyxin B: Experimental Study In Cells And Implications For Nursing Practice

2014 ◽  
Vol 48 (2) ◽  
pp. 272-277 ◽  
Author(s):  
Luciana Barros de Moura Neiva ◽  
Fernanda Teixeira Borges ◽  
Mirian Watanabe ◽  
Edson de Andrade Pessoa ◽  
Dulce Aparecida Barbosa ◽  
...  
Keyword(s):  
Fluorescent Dyes ◽  
Cell Damage ◽  
Kidney Injury ◽  
In Vitro Study ◽  
Polymyxin B ◽  
Concentration Cell ◽  
Tubular Cells ◽  
Risk Patients ◽  
Proximal Tubular

The aim of the study was to characterize the cell damage mechanisms involved in the pathophysiology of cytotoxicity of polymyxin B in proximal tubular cells (LLC - PK1) and discuss about the nurses interventions to identify at risk patients and consider prevention or treatment of nephrotoxicity acute kidney injury. This is a quantitative experimental in vitro study, in which the cells were exposed to 375μM polymyxin B sulfate concentration. Cell viability was determined by exclusion of fluorescent dyes and morphological method with visualization of apoptotic bodies for fluorescence microscopy. Cells exposed to polymyxin B showed reduced viability, increased number of apoptotic cells and a higher concentration of the enzyme lactate dehydrogenase. The administration of polymyxin B in vitro showed the need for actions to minimize adverse effects such as nephrotoxicity.


scholarly journals Canagliflozin protects against cisplatin-induced acute kidney injury by AMPK-mediated autophagy in renal proximal tubular cells

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Cheol Ho Park ◽  
Bin Lee ◽  
Myeonggil Han ◽  
Woo Joong Rhee ◽  
Man Sup Kwak ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protective Effect ◽  
Kidney Injury ◽  
Proximal Tubular Cells ◽  
Cell Viability Assay ◽  
Tubular Cells ◽  
Compound C ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

AbstractSodium-glucose cotransporter 2 inhibitors, which are recently introduced as glucose-lowering agents, improve cardiovascular and renal outcomes in patients with diabetes mellitus. These drugs also have beneficial effects in various kidney disease models. However, the effect of SGLT2 inhibitors on cisplatin-induced acute kidney injury (AKI) and their mechanism of action need to be elucidated. In this study, we investigated whether canagliflozin protects against cisplatin-induced AKI, depending on adenosine monophosphate-activated protein kinase (AMPK) activation and following induction of autophagy. In the experiments using the HK-2 cell line, cell viability assay and molecular analysis revealed that canagliflozin protected renal proximal tubular cells from cisplatin, whereas addition of chloroquine or compound C abolished the protective effect of canagliflozin. In the mouse model of cisplatin-induced AKI, canagliflozin protected mice from cisplatin-induced AKI. However, treatment with chloroquine or compound C in addition to administration of cisplatin and canagliflozin eliminated the protective effect of canagliflozin. Collectively, these findings indicate that canagliflozin protects against cisplatin-induced AKI by activating AMPK and autophagy in renal proximal tubular cells.

scholarly journals Chronic Kidney Diseases and Acute Kidney Injury in Patients With COVID-19: Evidence From a Meta-Analysis

2020 ◽  
Vol 7 ◽  
Author(s):  
Yangzhong Zhou ◽  
Qidong Ren ◽  
Gang Chen ◽  
Qiao Jin ◽  
Quexuan Cui ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Diseases ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Chronic Kidney Diseases

scholarly journals Renoprotective effects of a novel cMet agonistic antibody on kidney fibrosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yong Chul Kim ◽  
Junghun Lee ◽  
Jung Nam An ◽  
Jin Hyuk Kim ◽  
Young-Wook Choi ◽  
...  
Keyword(s):  
Kidney Diseases ◽  
Active Form ◽  
Kidney Injury ◽  
Biologically Active ◽  
Kidney Fibrosis ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
A Cell ◽  
Masson Trichrome Staining ◽  
Hepatocyte Growth

Abstract Hepatocyte growth factor (HGF) and its receptor, cMet, activate biological pathways necessary for repair and regeneration following kidney injury. Because HGF is a highly unstable molecule in its biologically active form, we asked whether a monoclonal antibody (Ab) that displays full agonist activity at the receptor could protect the kidney from fibrosis. We attempted to determine whether the cMet agonistic Ab might reduce fibrosis, the final common pathway for chronic kidney diseases (CKD). A mouse model of kidney fibrosis disease induced by unilateral ureteral obstruction was introduced and subsequently validated with primary cultured human proximal tubular epithelial cells (PTECs). In kidney biopsy specimens from patients with CKD, cMet immunohistochemistry staining showed a remarkable increase compared with patients with normal renal functions. cMet Ab treatment significantly increased the levels of phospho-cMet and abrogated the protein expression of fibrosis markers such as fibronectin, collagen 1, and αSMA as well as Bax2, which is a marker of apoptosis triggered by recombinant TGF-β1 in PTECs. Remarkably, injections of cMet Ab significantly prevented kidney fibrosis in obstructed kidneys as quantified by Masson trichrome staining. Consistent with these data, cMet Ab treatment decreased the expression of fibrosis markers, such as collagen1 and αSMA, whereas the expression of E-cadherin, which is a cell-cell adhesion molecule, was restored. In conclusion, cMet-mediated signaling may play a considerable role in kidney fibrosis. Additionally, the cMet agonistic Ab may be a valuable substitute for HGF because it is more easily available in a biologically active, stable, and purified form.

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