scholarly journals Organelle Stress and Crosstalk in Kidney Disease

Kidney360 ◽  
2020 ◽  
Vol 1 (10) ◽  
pp. 1155-1162
Author(s):  
Sho Hasegawa ◽  
Reiko Inagi
Keyword(s):  
Kidney Disease ◽  
Er Stress ◽  
Calcium Homeostasis ◽  
Stress Responses ◽  
Primary Cilia ◽  
Proximal Tubular Cells ◽  
Cellular Homeostasis ◽  
Tubular Cells ◽  
Progression Of Kidney Disease ◽  
Proximal Tubular

Organelles play important roles in maintaining cellular homeostasis. Organelle stress responses, especially in mitochondria, endoplasmic reticula (ER), and primary cilia, are deeply involved in kidney disease pathophysiology. Mitochondria are the center of energy production in most eukaryotic cells. Renal proximal tubular cells are highly energy demanding and abundant in mitochondria. Mitochondrial dysfunctions in association with energy metabolism alterations produce reactive oxygen species and promote inflammation in proximal tubular cells, resulting in progression of kidney disease. The ER play critical roles in controlling protein quality. Unfolded protein response (UPR) pathways are the adaptive response to ER stress for maintaining protein homeostasis. UPR pathway dysregulation under pathogenic ER stress often occurs in glomerular and tubulointerstitial cells and promotes progression of kidney disease. The primary cilia sense extracellular signals and maintain calcium homeostasis in cells. Dysfunction of the primary cilia in autosomal dominant polycystic kidney disease reduces the calcium concentration in proximal tubular cells, leading to increased cell proliferation and retention of cyst fluid. In recent years, the direct interaction at membrane contact sites has received increased attention in association with the development of imaging technologies. The part of the ER that is directly connected to mitochondria is termed the mitochondria-associated ER membrane (MAM), which regulates calcium homeostasis and phospholipid metabolism in cells. Disruption of MAM integrity collapses cellular homeostasis and leads to diseases such as diabetes and Alzheimer disease. This review summarizes recent research on organelle stress and crosstalk, and their involvement in kidney disease pathophysiology. In addition, potential treatment options that target organelle stress responses are discussed.

scholarly journals (−)-Epicatechin and the colonic metabolite 2,3-dihydroxybenzoic acid protect against high glucose and lipopolysaccharide-induced inflammation in renal proximal tubular cells through NOX-4/p38 signalling

2020 ◽  
Vol 11 (10) ◽  
pp. 8811-8824
Author(s):  
David Álvarez Cilleros ◽  
María Elvira López-Oliva ◽  
María Ángeles Martín ◽  
Sonia Ramos
Keyword(s):  
Kidney Disease ◽  
High Glucose ◽  
Diabetic Kidney Disease ◽  
Dihydroxybenzoic Acid ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Chronic Hyperglycaemia

Chronic hyperglycaemia and inflammation are present in diabetes and both processes have been related to the pathogenesis of diabetic kidney disease.

scholarly journals Advanced Oxidation Protein Products Induce Hypertrophy and Epithelial-To-Mesenchymal Transition in Human Proximal Tubular Cells through Induction of Endoplasmic Reticulum Stress

2015 ◽  
Vol 35 (2) ◽  
pp. 816-828 ◽  
Author(s):  
Xun Tang ◽  
Guang Rong ◽  
Yang Bu ◽  
Shaojie Zhang ◽  
Min Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Er Stress ◽  
Total Protein ◽  
Epithelial To Mesenchymal Transition ◽  
Proximal Tubular Cells ◽  
Advanced Oxidation Protein Products ◽  
Mesenchymal Transition ◽  
Tubular Cells ◽  
Cell Hypertrophy ◽  
Proximal Tubular

Background: In chronic kidney disease (CKD), the accumulation of advanced oxidation protein products (AOPPs) is prevalent. Hypertrophy and epithelial-to-mesenchymal transition (EMT) of tubular cells are associated with the pathogenesis of CKD. However, whether AOPPs induce tubular-cell hypertrophy and EMT is unclear. In this study, we investigated the effect of AOPPs on human proximal tubular cells (HK-2 cells) and the mechanisms underlying tubular-cell hypertrophy and EMT in vitro. Methods: The mRNA and protein expression of CCAAT/enhancer-binding protein-homologous protein (CHOP), glucose-regulated protein (GRP) 78, p27, α-smooth muscle actin (α-SMA) and E-cadherin were evaluated by quantitative real-time PCR and western blot, respectively. Cell cycle was detected by flow cytometry. Bicinchoninic acid method was performed to measure total protein content. Results: AOPP treatment upregulated total protein expression, caused an increase in the percentage of G1-phase cells, and induced the overexpression of p27 and α-SMA, lowered the expression of E-cadherin. Furthermore, AOPP treatment induced the overexpression of GRP78 and CHOP. Moreover, the aforementioned effects were reversed following the treatment of cells with an NADPH oxidase inhibitor, a reactive oxygen species (ROS) scavenger, or salubrinal, which is an inhibitor of ER stress, whereas these effects were produced after exposure to thapsigargin, an inducer of ER stress. Conclusion: Our results suggest that AOPPs induced HK-2-cell hypertrophy and EMT by inducing ER stress, which was likely mediated by ROS. These findings could facilitate the development of novel therapeutic strategies for suppressing the progression of CKD.

scholarly journals Abrogation of store-operated Ca2+ entry protects against crystal-induced ER stress in human proximal tubular cells

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Farai C. Gombedza ◽  
Samuel Shin ◽  
Yianni L. Kanaras ◽  
Bidhan C. Bandyopadhyay
Keyword(s):  
Er Stress ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

scholarly journals Potential Protection Effect of ER Homeostasis of N6-(2-Hydroxyethyl)adenosine Isolated from Cordyceps cicadae in Nonsteroidal Anti-Inflammatory Drug-Stimulated Human Proximal Tubular Cells

2021 ◽  
Vol 22 (4) ◽  
pp. 1577
Author(s):  
Charng-Cherng Chyau ◽  
Huei-Lin Wu ◽  
Chiung-Chi Peng ◽  
Shiau-Huei Huang ◽  
Chin-Chu Chen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Er Stress ◽  
Cell Damage ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Protein Levels ◽  
Cordyceps Cicadae ◽  
Proximal Tubular ◽  
Anti Inflammatory ◽  
Er Homeostasis

Nonsteroidal anti-inflammatory drugs (NSAIDs) belong to a class of universally and commonly used anti-inflammatory analgesics worldwide. A diversity of drawbacks of NSAIDs have been reported including cellular oxidative stress, which in turn triggers the accumulation of unfolded proteins, enhancing endoplasmic reticulum stress, and finally resulting in renal cell damage. Cordyceps cicadae (CC) has been used as a traditional medicine for improving renal function via its anti-inflammatory effects. N6-(2-hydroxyethyl)adenosine (HEA), a physiologically active compound, has been reported from CC mycelia (CCM) with anti-inflammatory effects. We hypothesize that HEA could protect human proximal tubular cells (HK–2) from NSAID-mediated effects on differential gene expression at the mRNA and protein levels. To verify this, we first isolated HEA from CCM using Sephadex® LH–20 column chromatography. The MTT assay revealed HEA to be nontoxic up to 100 µM toward HK–2 cells. The HK–2 cells were pretreated with HEA (10–20 µM) and then insulted with the NSAIDs diclofenac (DCF, 200 µM) and meloxicam (MXC, 400 µM) for 24 h. HEA (20 µM) effectively prevented ER stress by attenuating ROS production (p < 0.001) and gene expression of ATF–6, PERK, IRE1α, CDCFHOP, IL1β, and NFκB within 24 h. Moreover, HEA reversed the increase of GRP78 and CHOP protein expression levels induced by DCF and MXC, and restored the ER homeostasis. These results demonstrated that HEA treatments effectively protect against DCF- and MXC-induced ER stress damage in human proximal tubular cells through regulation of the GRP78/ATF6/PERK/IRE1α/CHOP pathway.

scholarly journals A Vaspin–HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Atsuko Nakatsuka ◽  
Satoshi Yamaguchi ◽  
Jun Eguchi ◽  
Shigeru Kakuta ◽  
Yoichiro Iwakura ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Obese Mice ◽  
Proximal Tubular Cells ◽  
Diabetic Kidney ◽  
Tubular Cells ◽  
Extracellular Release ◽  
Proximal Tubular ◽  
Visceral Adipose ◽  
Glucose Regulated Protein

AbstractProximal tubular cells (PTCs) are crucial for maintaining renal homeostasis, and tubular injuries contribute to progression of diabetic kidney disease (DKD). However, the roles of visceral adipose tissue-derived serine protease inhibitor (vaspin) in the development of DKD is not known. We found vaspin maintains PTCs through ameliorating ER stress, autophagy impairment, and lysosome dysfunction in DKD. Vaspin−/− obese mice showed enlarged and leaky lysosomes in PTCs associated with increased apoptosis, and these abnormalities were also observed in the patients with DKD. During internalization into PTCs, vaspin formed a complex with heat shock protein family A (Hsp70) member 1 like (HSPA1L) as well as 78 kDa glucose-regulated protein (GRP78). Both vaspin-partners bind to clathrin heavy chain and involve in the endocytosis. Notably, albumin-overload enhanced extracellular release of HSPA1L and overexpression of HSPA1L dissolved organelle stresses, especially autophagy impairment. Thus, vapsin/HSPA1L-mediated pathways play critical roles in maintaining organellar function of PTCs in DKD.

scholarly journals Correction: Abrogation of store-operated Ca2+ entry protects against crystal-induced ER stress in human proximal tubular cells

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Farai C. Gombedza ◽  
Samuel Shin ◽  
Yianni L. Kanaras ◽  
Bidhan C. Bandyopadhyay
Keyword(s):  
Er Stress ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

A Correction to this paper has been published: https://doi.org/10.1038/s41420-021-00445-9

ERK1/2 MAPK promotes autophagy to suppress ER stress-mediated apoptosis induced by cadmium in rat proximal tubular cells

2018 ◽  
Vol 52 ◽  
pp. 60-69 ◽  
Author(s):  
Tongwang Luo ◽  
Huiyan Zhang ◽  
Qi Yu ◽  
Gang Liu ◽  
Mengfei Long ◽  
...  
Keyword(s):  
Er Stress ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular

scholarly journals Impact of Diabetic Stress Conditions on Renal Cell Metabolome

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1141 ◽  
Author(s):  
Lagies ◽  
Bork ◽  
Kaminski ◽  
Troendle ◽  
Zimmermann ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Cell Lines ◽  
Diabetic Kidney Disease ◽  
Collecting Duct ◽  
Stress Conditions ◽  
Proximal Tubular Cells ◽  
Diabetic Kidney ◽  
Tubular Cells ◽  
Proximal Tubular

Diabetic kidney disease is a major complication in diabetes mellitus, and the most common reason for end-stage renal disease. Patients suffering from diabetes mellitus encounter glomerular damage by basement membrane thickening, and develop albuminuria. Subsequently, albuminuria can deteriorate the tubular function and impair the renal outcome. The impact of diabetic stress conditions on the metabolome was investigated by untargeted gas chromatography–mass spectrometry (GC-MS) analyses. The results were validated by qPCR analyses. In total, four cell lines were tested, representing the glomerulus, proximal nephron tubule, and collecting duct. Both murine and human cell lines were used. In podocytes, proximal tubular and collecting duct cells, high glucose concentrations led to global metabolic alterations in amino acid metabolism and the polyol pathway. Albumin overload led to the further activation of the latter pathway in human proximal tubular cells. In the proximal tubular cells, aldo-keto reductase was concordantly increased by glucose, and partially increased by albumin overload. Here, the combinatorial impact of two stressful agents in diabetes on the metabolome of kidney cells was investigated, revealing effects of glucose and albumin on polyol metabolism in human proximal tubular cells. This study shows the importance of including highly concentrated albumin in in vitro studies for mimicking diabetic kidney disease.

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