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https://www.readbyqxmd.com/read/29124787/reduced-tubular-degradation-of-glomerular-filtered-plasma-albumin-is-a-common-feature-in-acute-and-chronic-kidney-disease
#1
Yingjie Han, Nguyen D K Ly, Greg H Tesch, Philip Poronnik, David J Nikolic-Paterson
Tubular epithelial cells take up and degrade plasma albumin filtered by the glomerulus. Tubular damage resulting in reduced albumin uptake or degradation has been suggested as one mechanism contributing to albuminuria in kidney disease. This study investigated whether albumin uptake or degradation is altered in acute and chronic glomerular disease. Mouse models of acute glomerular injury (anti-GBM disease and LPS-induced albuminuria) and chronic disease (streptozotocin-induced diabetes and db/db mice) were examined...
November 10, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29109726/il-36%C3%AE-regulates-tubulointerstitial-inflammation-in-the-mouse-kidney
#2
Osamu Ichii, Junpei Kimura, Tadashi Okamura, Taro Horino, Teppei Nakamura, Hayato Sasaki, Yaser Hosny Ali Elewa, Yasuhiro Kon
IL-36α, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36α was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36α in kidney injury. IL-36α mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36α localized to dilated DTs. IL-36α expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29106063/cannabinoid-1-receptor-deletion-in-podocytes-mitigates-both-glomerular-and-tubular-dysfunction-in-a-mouse-model-of-diabetic-nephropathy
#3
Tony Jourdan, Joshua K Park, Zoltán V Varga, János Pálóczi, Nathan J Coffey, Avi Z Rosenberg, Grzegorz Godlewski, Resat Cinar, Ken Mackie, Pal Pacher, George Kunos
AIMS: To determine the specific role of podocyte-expressed cannabinoid-1 receptor (CB1 R) in the development of diabetic nephropathy (DN), relative to CB1 R in other renal cell types. MATERIAL AND METHODS: We developed a mouse model with a podocyte-specific deletion of CB1 R (pCB1Rko) and challenged this model with streptozotocin (STZ)-induced type-1 DN. We also assessed the podocyte response to high glucose in vitro and its effects on CB1 R activation. RESULTS: High glucose exposure for 48h led to an increase in CB1 R gene expression (CNR1) and endocannabinoid production in cultured human podocytes...
November 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29065889/injury-induced-expression-of-caveolar-proteins-in-human-kidney-tubules-role-of-megakaryoblastic-leukemia-1
#4
Krzysztof M Krawczyk, Jennifer Hansson, Helén Nilsson, Katarzyna K Krawczyk, Karl Swärd, Martin E Johansson
BACKGROUND: Caveolae are membrane invaginations measuring 50-100 nm. These organelles, composed of caveolin and cavin proteins, are important for cellular signaling and survival. Caveolae play incompletely defined roles in human kidneys. Induction of caveolin-1/CAV1 in diseased tubules has been described previously, but the responsible mechanism remains to be defined. METHODS: Healthy and atrophying human kidneys were stained for caveolar proteins, (caveolin 1-3 and cavin 1-4) and examined by electron microscopy...
October 24, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29042455/microrna-709-mediates-acute-tubular-injury-through-effects-on-mitochondrial-function
#5
Yan Guo, Jiajia Ni, Shuang Chen, Mi Bai, Jiajuan Lin, Guixia Ding, Yue Zhang, Pingping Sun, Zhanjun Jia, Songming Huang, Li Yang, Aihua Zhang
Mitochondrial dysfunction has important roles in the pathogenesis of AKI, yet therapeutic approaches to improve mitochondrial function remain limited. In this study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was significantly upregulated in the proximal tubular cells (PTCs). The expression of miR-709 in the renal PTCs of patients with AKI correlated with the severity of kidney injury...
October 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29037855/nephrosphere-derived-cells-are-induced-to-multilineage-differentiation-when-cultured-on-human-decellularized-kidney-scaffolds
#6
Silvia Bombelli, Chiara Meregalli, Carla Scalia, Giorgio Bovo, Barbara Torsello, Sofia De Marco, Massimiliano Cadamuro, Paolo Viganò, Guido Strada, Giorgio Cattoretti, Cristina Bianchi, Roberto A Perego
In end-stage chronic kidney disease, the option of organ transplantation is limited because of the scarce availability of kidneys. The combination of stem cell research, regenerative medicine, and tissue engineering seems a promising approach to produce new transplantable kidneys. Currently, the possibility to repopulate naturally obtained scaffolds with cells of different sources is advancing. Our aim was to test, for the first time, whether the nephrosphere (NS) cells, composed by renal stem/progenitor-like cells, were able to repopulate different nephron portions of renal extracellular matrix scaffolds obtained after decellularization of human renal tissue slices...
October 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29032370/an-immunofluorescence-assay-for-extracellular-matrix-components-highlights-the-role-of-epithelial-cells-in-producing-a-stable-fibrillar-extracellular-matrix
#7
Omar S Qureshi, Hélène Bon, Breda Twomey, Gill Holdsworth, Kirsty Ford, Marianne Bergin, Linghong Huang, Mariusz Muzylak, Louise J Healy, Vanessa Hurdowar, Timothy S Johnson
Activated fibroblasts are considered major drivers of fibrotic disease progression through the production of excessive extracellular matrix (ECM) in response to signals from damaged epithelial and inflammatory cells. Nevertheless, epithelial cells are capable of expressing components of the ECM, cross-linking enzymes that increase its stability and are sensitive to factors involved in the early stages of fibrosis. We therefore wanted to test the hypothesis that epithelial cells can deposit ECM in response to stimulation in a comparable manner to fibroblasts...
October 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28994737/anti-inflammatory-pyranochalcone-derivative-attenuates-lps-induced-acute-kidney-injury-via-inhibiting-tlr4-nf-%C3%AE%C2%BAb-pathway
#8
Min Shi, Xiaoxi Zeng, Fan Guo, Rongshuang Huang, Yanhuan Feng, Liang Ma, Li Zhou, Ping Fu
Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound 5b was derived from natural pyranochalcones and exhibited potent anti-inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the renoprotective effects and potential mechanism of 5b against lipopolysaccharide (LPS)-induced AKI. C57BL/6 mice and human renal proximal tubule cell line (HK-2 cell) were treated with LPS, respectively...
October 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28993506/kidney-proximal-tubule-lipoapoptosis-is-regulated-by-fatty-acid-transporter-2-fatp2
#9
Shenaz Khan, Pablo D Cabral, William P Schilling, Zachary W Schmidt, Asif N Uddin, Amelia Gingras, Sethu M Madhavan, Jeffrey L Garvin, Jeffrey R Schelling
Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across the damaged glomerular filtration barrier and subsequent reabsorption by the downstream proximal tubule, causing lipoapoptosis. We sought to identify the apical proximal tubule transporter that mediates NEFA uptake and cytotoxicity. We observed transporter-mediated uptake of fluorescently labeled NEFA in cultured proximal tubule cells and microperfused rat proximal tubules, with greater uptake from the apical surface than from the basolateral surface...
October 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28990525/a-human-proximal-tubular-epithelial-cell-model-to-explore-a-knowledge-gap-on-neonatal-drug-disposition
#10
Ahmed Reda, Anke Raaijmakers, Saskia van Dorst, Charlotte G G M Pauwels, Karel Allegaert, Mohamed A Elmonem, Rosalinde Masereeuw, Lambertus van den Heuvel, Elena Levtchenko, Fanny Oliveira Arcolino
BACKGROUND: Finding the right drug-dosage for neonates is still a challenge. Until now, neonatal doses are extrapolated from adults and children doses. However, there are differences between neonatal and adult kidney physiology that should be considered, especially when it comes to drug metabolism and/or transport. Studying renal drug disposition in neonates is limited by the lack of reliable human cell models. OBJECTIVE: To illustrate the feasibility of developing an in vitro model for neonatal proximal tubule epithelial cells (nPTECs) to study renal drug disposition at this age...
October 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28979210/chronic-hypobaric-hypoxia-modulates-primary-cilia-differently-in-adult-and-fetal-ovine-kidneys
#11
Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T Sherpa, Rajasekharreddy Pala, Kimberly F Atkinson, William J Pearce, Lubo Zhang, Surya M Nauli
Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28977780/urinary-mirnas-as-biomarkers-for-noninvasive-evaluation-of-radiation-induced-renal-tubular-injury
#12
Sagar Bhayana, Feifei Song, Jidhin Jacob, Paolo Fadda, Nicholas C Denko, Meng Xu-Welliver, Arnab Chakravarti, Naduparambil K Jacob
Radiation nephropathy is one of the common late effects in cancer survivors who received radiotherapy as well as in victims of radiation accidents. The clinical manifestations of radiation nephropathy occur months after exposure. To date, there are no known early biomarkers to predict the future development of radiation nephropathy. This study focuses on the development of urinary biomarkers providing readout of acute responses in renal tubular epithelial cells. An amplification-free hybridization-based nCounter assay was used to detect changes in mouse urinary miRNAs after irradiation...
October 4, 2017: Radiation Research
https://www.readbyqxmd.com/read/28929120/sulodexide-protects-renal-tubular-epithelial-cells-from-oxidative-stress-induced-injury-via-upregulating-klotho-expression-at-an-early-stage-of-diabetic-kidney-disease
#13
Yu Ning Liu, Jingwei Zhou, Tingting Li, Jing Wu, Shu Hua Xie, Hua-Feng Liu, Zhangsuo Liu, Tae Sun Park, Yaoxian Wang, Wei Jing Liu
The hypoalbuminuric effect of sulodexide (SDX) on diabetic kidney disease (DKD) was suggested by some clinical trials but was denied by the Collaborative Study Group. In this study, the diabetic rats were treated with SDX either from week 0 to 24 or from week 13 to 24. We found that 24-week treatment significantly decreased the urinary protein and HAVCR1 excretion, inhibited the interstitial expansion, and downregulated the renal cell apoptosis and interstitial fibrosis. Renoprotection was also associated with a reduction in renocortical/urinary oxidative activity and the normalization of renal klotho expression...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28903918/-pro-renin-receptor-mediates-albumin-induced-cellular-responses-role-of-site-1-protease-derived-soluble-pro-renin-receptor-in-renal-epithelial-cells
#14
Hui Fang, Chuanming Xu, Aihua Lu, Chang-Jiang Zou, Shiying Xie, Yanting Chen, Li Zhou, Mi Liu, Lei Wang, Weidong Wang, Tianxin Yang
Proteinuria is a characteristic of chronic kidney disease (CKD) and also a causative factor that promotes the disease progression in part via activation of intrarenal renin-angiotensin system (RAS). (Pro) renin receptor (PRR), a newly discovered component of the RAS, binds renin and (pro) renin to promote angiotensin I generation. The present study was performed to test the role of soluble PRR (sPRR) in albumin overload-induced responses in cultured human renal proximal tubular cell line HK-2 cells. Bovine serum albumin (BSA) treatment for 24 h at 20 mg/ml induced renin activity and inflammation, both of which were attenuated by a PRR decoy inhibitor PRO20...
September 13, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28894140/d-serine-a-novel-uremic-toxin-induces-senescence-in-human-renal-tubular-cells-via-gcn2-activation
#15
Akira Okada, Masaomi Nangaku, Tzu-Ming Jao, Hiroshi Maekawa, Yu Ishimono, Takahisa Kawakami, Reiko Inagi
The prevalence of chronic kidney disease (CKD), characterized by progressive renal dysfunction with tubulointerstitial fibrosis, is increasing because of societal aging. Uremic toxins, accumulated during renal dysfunction, cause kidney damage, leading to renal deterioration. A recent metabolomic analysis revealed that plasma D-serine accumulation is associated with faster progression of renal dysfunction in CKD patients. However, the causal relationship and the underlying mechanisms remain unclear. Herein, we demonstrated that D-serine markedly induced cellular senescence and apoptosis in a human proximal tubular cell line, HK-2, and primary culture of human renal tubular cells...
September 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28875561/enhanced-peripheral-nerve-regeneration-through-asymmetrically-porous-nerve-guide-conduit-with-nerve-growth-factor-gradient
#16
Se Heang Oh, Jun Goo Kang, Tae Ho Kim, Uk Namgung, Kyu Sang Song, Byeong Hwa Jeon, Jin Ho Lee
In this study, we fabricated a nerve guide conduit (NGC) with nerve growth factor (NGF) gradient along the longitudinal direction by rolling a porous polycaprolactone (PCL) membrane with NGF concentration gradient. The NGF immobilized on the membrane was continuously released for up to 35 days, and the released amount of the NGF from the membrane gradually increased from the proximal to distal NGF ends, which may allow a neurotrophic factor gradient in the tubular NGC for a sufficient period. From the in vitro cell culture experiment, it was observed that the PC12 cells sense the NGF concentration gradient on the membrane for the cell proliferation and differentiation...
September 5, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28852062/farnesoid-x-receptor-activation-protects-the-kidney-from-ischemia-reperfusion-damage
#17
Zhibo Gai, Lei Chu, Zhenqiang Xu, Xiaoming Song, Dongfeng Sun, Gerd A Kullak-Ublick
Farnesoid X receptor (FXR) activation has been reported to reduce inflammation and oxidative stress. Because both inflammation and oxidative stress are critical for tissue destruction during kidney ischemia reperfusion (I/R) injury, we investigated the protective role of FXR against kidney damage induced by I/R in mice. Mice undergoing renal I/R developed the typical features of acute kidney injury (AKI): increased creatinine, albuminuria, tubular necrosis and apoptosis. Inflammatory cytokine production and oxidative stress were also markedly increased...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811645/inhibin-a-and-decorin-secreted-by-human-adult-renal-stem-progenitor-cells-through-the-tlr2-engagement-induce-renal-tubular-cell-regeneration
#18
Fabio Sallustio, Claudia Curci, Alessandra Aloisi, Chiara Cristina Toma, Elisabetta Marulli, Grazia Serino, Sharon Natasha Cox, Giuseppe De Palma, Alessandra Stasi, Chiara Divella, Rosaria Rinaldi, Francesco Paolo Schena
Acute kidney injury (AKI) is a public health problem worldwide. Several therapeutic strategies have been made to accelerate recovery and improve renal survival. Recent studies have shown that human adult renal progenitor cells (ARPCs) participate in kidney repair processes, and may be used as a possible treatment to promote regeneration in acute kidney injury. Here, we show that human tubular ARPCs (tARPCs) protect physically injured or chemically damaged renal proximal tubular epithelial cells (RPTECs) by preventing cisplatin-induced apoptosis and enhancing proliferation of survived cells...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715434/engineered-extracellular-matrices-with-controlled-mechanics-modulate-renal-proximal-tubular-cell-epithelialization
#19
Jeffrey A Beamish, Evan Chen, Andrew J Putnam
Acute kidney injury (AKI) is common and associated with significant morbidity and mortality. Recovery from many forms of AKI involves the proliferation of renal proximal tubular epithelial cells (RPTECs), but the influence of the microenvironment in which this recovery occurs remains poorly understood. Here we report the development of a poly(ethylene glycol) (PEG) hydrogel platform to study the influence of substrate mechanical properties on the proliferation of human RPTECs as a model for recovery from AKI...
2017: PloS One
https://www.readbyqxmd.com/read/28705935/forkhead-box-o3-foxo3-regulates-kidney-tubular-autophagy-following-urinary-tract-obstruction
#20
COMPARATIVE STUDY
Ling Li, Ronald Zviti, Catherine Ha, Zhao V Wang, Joseph A Hill, Fangming Lin
Autophagy has been shown to be important for normal homeostasis and adaptation to stress in the kidney. Yet, the molecular mechanisms regulating renal epithelial autophagy are not fully understood. Here, we explored the role of the stress-responsive transcription factor forkhead box O3 (FoxO3) in mediating injury-induced proximal tubular autophagy in mice with unilateral ureteral obstruction (UUO). We show that following UUO, FoxO3 is activated and displays nuclear expression in the hypoxic proximal tubules exhibiting high levels of autophagy...
August 18, 2017: Journal of Biological Chemistry
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