Ezra Kombo Osoro, Xiaojuan Du, Dong Liang, Xi Lan, Riaz Farooq, Fumeng Huang, Wenhua Zhu, Jiajun Ren, Muhammad Sadiq, Lifang Tian, Xudong Yang, Dongmin Li, Shemin Lu
The precise molecular mechanism of autophagy dysfunction in type 1 diabetes is not known. Herein, the role of programmed cell death 4 (PDCD4) in autophagy regulation in the pathogenesis of diabetic kidney disease (DKD) in vivo and in vitro was described. It was found that Pdcd4 mRNA and protein was upregulated in the streptozotocin (STZ)-induced DKD rats. In addition, a unilateral ureteral obstruction mouse model displayed an upregulation of PDCD4 in the disease group. kidney biopsy samples of human DKD patients showed an upregulation of PDCD4...
April 8, 2021: Biochemistry and Cell Biology
Minolfa C Prieto, Alexis A Gonzalez, Bruna Visniauskas, L Gabriel Navar
The intrarenal renin-angiotensin system is critical for the regulation of tubule sodium reabsorption, renal haemodynamics and blood pressure. The excretion of renin in urine can result from its increased filtration, the inhibition of renin reabsorption by megalin in the proximal tubule, or its secretion by the principal cells of the collecting duct. Modest increases in circulating or intrarenal angiotensin II (ANGII) stimulate the synthesis and secretion of angiotensinogen in the proximal tubule, which provides sufficient substrate for collecting duct-derived renin to form angiotensin I (ANGI)...
April 6, 2021: Nature Reviews. Nephrology
Hewang Lee, Xiaoliang Jiang, Imran Perwaiz, Peiying Yu, Jin Wang, Ying Wang, Maik Hüttemann, Robin A Felder, David R Sibley, Brian M Polster, Selim Rozyyev, Ines Armando, Zhiwei Yang, Peng Qu, Pedro A Jose
Overproduction of reactive oxygen species (ROS) plays an important role in the pathogenesis of hypertension. The dopamine D5 receptor (D5 R) is known to decrease ROS production, but the mechanism is not completely understood. In HEK293 cells overexpressing D5 R, fenoldopam, an agonist of the two D1 -like receptors, D1 R and D5 R, decreased the production of mitochondria-derived ROS (mito-ROS). The fenoldopam-mediated decrease in mito-ROS production was mimicked by Sp-cAMPS but blocked by Rp-cAMPS. In human renal proximal tubule cells with DRD1 gene silencing to eliminate the confounding effect of D1 R, fenoldopam still decreased mito-ROS production...
April 5, 2021: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Kristin I Bender, Laura L Schwartz, Ariel Cohen, Claudia Mosquera Vasquez, Matthew J Murtha, Tad Eichler, Jason P Thomas, Ashley R Jackson, John D Spencer
Antimicrobial peptides are essential host defense mechanisms that prevent urinary tract infections. Recent studies demonstrate that peptides in the Ribonuclease A Superfamily have antimicrobial activity against uropathogens and protect the urinary tract from uropathogenic Escherichia coli (UPEC). Little is known is about the antibacterial function or expression of Ribonuclease 4 in the human urinary tract. Here, we show that full-length recombinant Ribonuclease 4 peptide and synthetic amino-terminal Ribonuclease 4 peptide fragment have antibacterial activity against UPEC and multi-drug resistant UPEC...
April 5, 2021: American Journal of Physiology. Renal Physiology
Leixi Xue, Yi Zhang, Jiajun Xu, Wentian Lu, Qing Wang, Jinxiang Fu, Zhichun Liu
Purpose: Current studies on the mechanism of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) in lupus nephritis (LN) mainly focus on the inflammatory pathway. Herein, we aimed to determine whether TWEAK could promote the progression of renal interstitial fibrosis by regulating peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) expression and intervening in lipid metabolism in LN. Materials and Methods: MRL/lpr mice, an animal model of lupus, were treated with the anti-TWEAK antibody or co-treated with adeno-associated virus-mediated PGC-1α short hairpin RNA (shRNA)...
2021: Journal of Inflammation Research
Yu Rohovyi, V Tsitrin, L Arkchipova, V Bilookyi, O Kolesnik
Objective - to find out the possibility of using molecular hydrogen in the correction of no-reflow syndrome in the polyuric stage of acute kidney injury 72 hours after the administration of mercuric chloride in rats on a hyposodium diet. The experiments were performed on 60 male white non-linear sexually mature rats weighing 0.16-0.18 kg to study the effect of water loading with saturation with molecular hydrogen. Sublimate nephropathy was modeled under conditions of a hyposodium diet by subcutaneous injection of 0...
February 2021: Georgian Medical News
Eric R Barros Lamus, Valentina Carotti, Christine R S de Vries, Femke Witsel, Onno J Arntz, Fons A J van de Loo, Cristian A Carvajal, René J M Bindels, Joost G J Hoenderop, Juan P Rigalli
Purinergic signaling regulates several renal physiological and pathophysiological processes. Extracellular vesicles (EVs) are nanoparticles released by most cell types, which, in non-renal tissues, modulate purinergic signaling. The aim of this study was to investigate the effect of EVs from renal proximal tubule (HK2) and collecting duct cells (HCD) on intra- and intersegment modulation of extracellular ATP levels, the underlying molecular mechanisms, and the impact on the expression of the alpha subunit of the epithelial sodium channel (αENaC)...
May 2021: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Karl P Schlingmann, Aparna Renigunta, Ewout J Hoorn, Anna-Lena Forst, Vijay Renigunta, Velko Atanasov, Sinthura Mahendran, Tahsin Stefan Barakat, Valentine Gillion, Nathalie Godefroid, Alice S Brooks, Dorien Lugtenberg, Jennifer Lake, Huguette Debaix, Christoph Rudin, Bertrand Knebelmann, Stephanie Tellier, Caroline Rousset-Rouvière, Daan Viering, Jeroen H F deBaaij, Stefanie Weber, Oleg Palygin, Alexander Staruschenko, Robert Kleta, Pascal Houillier, Detlef Bockenhauer, Olivier Devuyst, Rosa Vargas-Poussou, Richard Warth, Anselm A Zdebik, Martin Konrad
BACKGROUND: The transepithelial transport of electrolytes, solutes, and water in the kidney is a well-orchestrated process involving numerous membrane transport systems. Basolateral potassium channels in tubular cells not only mediate potassium recycling for proper Na+ ,K+ -ATPase function but are also involved in potassium and pH sensing. Genetic defects in KCNJ10 cause EAST/SeSAME syndrome, characterized by renal salt wasting with hypokalemic alkalosis associated with epilepsy, ataxia, and sensorineural deafness...
April 2, 2021: Journal of the American Society of Nephrology: JASN
Young-Ah Kim, Hyun-Ju Kim, Mi-Gyeong Gwon, Hyemin Gu, Hyun-Jin An, Seongjae Bae, Jaechan Leem, Hyun Jin Jung, Kwan-Kyu Park
Autophagy in the proximal tubules may promote fibrosis by activating tubular cell death, interstitial inflammation, and the production of pro-fibrotic factors. The signal transducer and activator of transcription 3 (STAT3) is activated as a potential transcription factor, which mediates the stimulation of renal fibrosis. We investigated the role of the STAT3 in autophagy and its effect on the prevention of interstitial renal fibrosis. In this study, we use synthesized STAT3 decoy oligonucleotides (ODN), which were injected into the tail veins of unilateral ureteral obstruction (UUO) mice, to explore the regulation of autophagy in UUO-induced renal fibrosis...
March 25, 2021: Biomedicines
Zaher Armaly, Safa Kinaneh, Karl Skorecki
Corona virus disease 2019 (COVID-19) imposes a serious public health pandemic affecting the whole world, as it is spreading exponentially. Besides its high infectivity, SARS-CoV-2 causes multiple serious derangements, where the most prominent is severe acute respiratory syndrome as well as multiple organ dysfunction including heart and kidney injury. While the deleterious impact of SARS-CoV-2 on pulmonary and cardiac systems have attracted remarkable attention, the adverse effects of this virus on the renal system is still underestimated...
March 15, 2021: Journal of Clinical Medicine
Gerald Schwerdt, Michael Kopf, Michael Gekle
The kidney is threatened by a lot of potentially toxic substances. To study the influence of the nephrotoxin ochratoxin A (OTA) we established a cell co-culture model consisting of human renal proximal tubule cells and fibroblasts. We studied the effect of OTA on cell survival, the expression of genes and/or proteins related to cell death, extracellular matrix and energy homeostasis. OTA-induced necrosis was enhanced in both cell types in the presence of the respective other cell type, whereas OTA-induced apoptosis was independent therefrom...
March 18, 2021: Toxins
Eugenia Awuah Boadi, Samuel Shin, Samuel Yeroushalmi, Bok-Eum Choi, Peijun Li, Bidhan C Bandyopadhyay
Proximal tubular (PT) acidosis, which alkalinizes the urinary filtrate, together with Ca2+ supersaturation in PT can induce luminal calcium phosphate (CaP) crystal formation. While such CaP crystals are known to act as a nidus for CaP/calcium oxalate (CaOx) mixed stone formation, the regulation of PT luminal Ca2+ concentration ([Ca2+ ]) under elevated pH and/or high [Ca2+ ] conditions are unknown. Since we found that transient receptor potential canonical 3 (TRPC3) knockout (KO; -/-) mice could produce mild hypercalciuria with CaP urine crystals, we alkalinized the tubular pH in TRPC3-/- mice by oral acetazolamide (0...
March 17, 2021: International Journal of Molecular Sciences
Paul E Squires, Gareth W Price, Ulrik Mouritzen, Joe A Potter, Bethany M Williams, Claire E Hills
Chronic kidney disease (CKD) is a global health problem associated with a number of comorbidities. Recent evidence implicates increased hemichannel-mediated release of adenosine triphosphate (ATP) in the progression of tubulointerstitial fibrosis, the main underlying pathology of CKD. Here, we evaluate the effect of danegaptide on blocking hemichannel-mediated changes in the expression and function of proteins associated with disease progression in tubular epithelial kidney cells. Primary human proximal tubule epithelial cells (hPTECs) were treated with the beta1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± danegaptide...
March 10, 2021: International Journal of Molecular Sciences
Linda Awdishu, Amy Le, Jordan Amato, Vidhyut Jani, Soma Bal, Robert H Mills, Marvic Carrillo-Terrazas, David J Gonzalez, Ashita Tolwani, Anjali Acharya, Jorge Cerda, Melanie S Joy, Paola Nicoletti, Etienne Macedo, Sucheta Vaingankar, Ravindra Mehta, Satish P RamachandraRao, On Behalf Of The Direct Investigators
BACKGROUND: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcus aureus . Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses...
March 10, 2021: International Journal of Molecular Sciences
Carlos Arias-Cabrales, Eva Rodriguez-Garcia, Javier Gimeno, David Benito, María José Pérez-Sáez, Dolores Redondo-Pachón, Anna Buxeda, Carla Burballa, Marta Crespo, Marta Riera, Julio Pascual
The role of C5a receptors (C5aR1 and C5L2) in renal ischemia-reperfusion injury (IRI) is uncertain. We generated an in vitro model of hypoxia/reoxygenation with human proximal tubule epithelial cells to mimic some IRI events. C5aR1, membrane attack complex (MAC) and factor H (FH) deposits were evaluated with immunofluorescence. Quantitative polymerase chain reaction evaluated the expression of C5aR1 , C5L2 genes as well as genes related to tubular injury, inflammation, and profibrotic pathways. Additionally, C5aR1 and C5L2 deposits were evaluated in kidney graft biopsies (KB) from transplant patients with delayed graft function (DGF, n = 12) and compared with a control group ( n = 8)...
March 2, 2021: Journal of Clinical Medicine
Roger Pamphlett, Philip A Doble, David P Bishop
The kidney plays a dominant role in the pathogenesis of essential hypertension, but the initial pathogenic events in the kidney leading to hypertension are not known. Exposure to mercury has been linked to many diseases including hypertension in epidemiological and experimental studies, so we studied the distribution and prevalence of mercury in the human kidney. Paraffin sections of kidneys were available from 129 people ranging in age from 1 to 104 years who had forensic/coronial autopsies. One individual had injected himself with metallic mercury, the other 128 were from varied clinicopathological backgrounds without known exposure to mercury...
March 21, 2021: Toxics
Ivana Solic, Anita Racetin, Natalija Filipovic, Snjezana Mardesic, Ivana Bocina, Danica Galesic-Ljubanovic, Meri Glavina Durdov, Mirna Saraga-Babić, Katarina Vukojevic
The spatiotemporal expression of α-tubulin, inversin and dishevelled-1 (DVL-1) proteins associated with the Wnt-signaling pathway, and primary cilia morphology were analyzed in developing kidneys (14th-38th developmental weeks), healthy postnatal (1.5- and 7-years old) and pathologically changed human kidneys, including multicystic dysplastic kidneys (MCDK), focal segmental glomerulosclerosis (FSGS) and nephrotic syndrome of the Finnish type (CNF). The analysis was performed by double immunofluorescence, electron microscopy, semiquantitative and statistical methods...
March 28, 2021: International Journal of Molecular Sciences
Stefanny M Figueroa, Patricio Araos, Javier Reyes, Basile Gravez, Jonatan Barrera-Chimal, Cristián A Amador
Renal diseases are a global health concern, and nearly 24% of kidney disease patients are overweight or obese. Particularly, increased body mass index has been correlated with oxidative stress and urinary albumin excretion in kidney disease patients, also contributing to increased cardiovascular risk. Albumin is the main plasma protein and is able to partially cross the glomerular filtration barrier, being reabsorbed mainly by the proximal tubule through different mechanisms. However, it has been demonstrated that albumin suffers different posttranslational modifications, including oxidation, which appears to be tightly linked to kidney damage progression and is increased in obese patients...
March 8, 2021: Antioxidants (Basel, Switzerland)
Haixia Fu, Debo Chu, Xiuli Geng
MiR-17 is found upregulated in diabetic mice; however, its effect(s) on renal fibrosis of diabetic nephropathy remain(s) unknown. This study aimed to explore the mechanism underlying the downregulation of miR-17 in renal fibrosis of diabetic nephropathy (DN). Patients with diabetes mellitus (DM) and DN and normal healthy individual controls, mice (db/db, db/m), and human mesangial cells (HMCs) and human proximal tubule epithelial cells (HK-2) were used as research subjects in the study. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to measure the expression of miR-17 in the serum samples, renal tissues and cells...
April 2, 2021: Molecular and Cellular Biochemistry
Mallory L Downie, R Todd Alexander
The majority of calcium filtered by the glomerulus is reabsorbed along the nephron. Most is reabsorbed from the proximal tubule (> 60%) via a paracellular pathway composed of the tight junction proteins claudins-2 and -12, a process driven by sodium and consequently water reabsorption. The thick ascending limb reabsorbs the next greatest amount of calcium (20-25%), also by a paracellular pathway composed of claudins-16 and -19. This pathway is regulated by the CaSR, whose activity increases the expression of claudin-14, a protein that blocks paracellular calcium reabsorption...
April 1, 2021: Pediatric Nephrology
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