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https://www.readbyqxmd.com/read/29038896/inducible-atf3-nfat-axis-aggravates-podocyte-injury
#1
Hong Zhang, Shun Liang, Yue Du, Ruizhao Li, Chaosheng He, Wenjian Wang, Shuangxin Liu, Zhiming Ye, Xinling Liang, Wei Shi, Bin Zhang
Podocyte injury and loss contribute to proteinuria, glomerulosclerosis, and eventually kidney failure. Activating transcription factor 3 (ATF3) is a stress inducible transcription factor that is transiently expressed following stimulation. However, we show for the first time an induction of ATF3 in podocytes from patients with chronic kidney disease, including minimal change disease, focal segmental glomerulosclerosis, and diabetic nephropathy. The role of ATF3 induction in podocytes under chronic conditions is currently unknown...
October 16, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29038887/mutations-in-inf2-may-be-associated-with-renal-histology-other-than-focal-segmental-glomerulosclerosis
#2
Anja K Büscher, Nora Celebi, Peter F Hoyer, Hanns-Georg Klein, Stefanie Weber, Julia Hoefele
BACKGROUND: In 2010, INF2 mutations were associated with autosomal-dominant focal segmental glomerulosclerosis (FSGS), clinically presenting with moderate proteinuria in adolescence. However, in the meantime, cases with more severe clinical courses have been described, including progression to end-stage renal disease (ESRD) during childhood. INF2 mutations in patients with isolated FSGS are clustered in exons 2 to 4, encoding the diaphanous inhibitory domain, involved in the regulation of the podocyte actin cytoskeleton...
October 6, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29038743/mature-induced-pluripotent-stem-cell-derived-human-podocytes-reconstitute-kidney-glomerular-capillary-wall-function-on-a-chip
#3
Samira Musah, Akiko Mammoto, Thomas C Ferrante, Sauveur S F Jeanty, Mariko Hirano-Kobayashi, Tadanori Mammoto, Kristen Roberts, Seyoon Chung, Richard Novak, Miles Ingram, Tohid Fatanat-Didar, Sandeep Koshy, James C Weaver, George M Church, Donald E Ingber
An in vitro model of the human kidney glomerulus - the major site of blood filtration - could facilitate drug discovery and illuminate kidney-disease mechanisms. Microfluidic organ-on-a-chip technology has been used to model the human proximal tubule, yet a kidney-glomerulus-on-a-chip has not been possible because of the lack of functional human podocytes - the cells that regulate selective permeability in the glomerulus. Here, we demonstrate an efficient (> 90%) and chemically defined method for directing the differentiation of human induced pluripotent stem (hiPS) cells into podocytes that express markers of the mature phenotype (nephrin+, WT1+, podocin+, Pax2-) and that exhibit primary and secondary foot processes...
2017: Nature biomedical engineering
https://www.readbyqxmd.com/read/29035194/clinicopathologic-characteristics-of-light-chain-proximal-tubulopathy-with-light-chain-inclusions-involving-multiple-renal-cell-types%C3%A2
#4
Xiaomei Li, Feng Xu, Dandan Liang, Shaoshan Liang, Xiaodong Zhu, Mingchao Zhang, Xianghua Huang, Zhihong Liu, Caihong Zeng
Light chain proximal tubulopathy (LCPT) associated with plasma cell dyscrasias is a rare abnormality, especially cases involving multiple cell types. The aim of this study is to explore the characteristics and outcomes of these diseases. We comprehensively evaluated the clinical-pathological data, treatment, and outcomes of 6 LCPT patients with involvement of multiple cell types. In 3 cases, we found that the inclusions largely existed in tubular cells, while in 2 cases they coexisted in podocytes and tubular cells, and in 1 case they coexisted in histiocytes and tubular cells...
October 16, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/29035193/renal-outcome-in-iga-nephropathy-according-to-oxford-classification-and-ultrastructural-analysis-in-a-brazilian-center%C3%A2
#5
Giovana Mariani, Leandro L L Freitas, Ricardo L Zollner, Maria Almerinda V F Ribeiro Alves
AIMS: Correlate clinical and histologic features with renal outcome in patients with biopsy-proven IgA nephropathy (IgAN). MATERIALS AND METHODS: Retrospective analysis of records and renal tissue of IgAN patients. Histology was revised according to MEST score of Oxford classification. Focal segmental glomerulosclerosis (FSGS) features were assessed by light microscopy. Electron microscopy review searched for podocyte effacement. RESULTS: 67 patients were included, 56...
October 16, 2017: Clinical Nephrology
https://www.readbyqxmd.com/read/29033543/effect-of-echinacoside-on-kidney-fibrosis-by-inhibition-of-tgf-%C3%AE-1-smads-signaling-pathway-in-the-db-db-mice-model-of-diabetic-nephropathy
#6
Fengjuan Tang, Yarong Hao, Xue Zhang, Jian Qin
Kidney fibrosis and renal tubular epithelial-to-mesenchymal transition (EMT) are the main pathological changes of diabetic nephropathy (DN), which eventually leads to end-stage renal disease. Previous studies have suggested that echinacoside (ECH) is antifibrotic in the liver. However, the effect of ECH on kidney fibrosis in DN and its mechanisms are unknown. This study was performed to explore the effect of ECH on kidney fibrosis and also the molecular mechanisms of ECH in a db/db mice model of DN. Our results showed that, relative to db/db mice, the mice in the ECH group had an improved general state and reduced blood glucose and 24-hour urinary protein levels...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29026873/graft-growth-and-podocyte-dedifferentiation-in-donor-recipient-size-mismatch-kidney-transplants
#7
Janina Müller-Deile, Jan Hinrich Bräsen, Marion Pollheimer, Manfred Ratschek, Hermann Haller, Lars Pape, Mario Schiffer
BACKGROUND: Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. METHODS: We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient...
October 2017: Transplantation Direct
https://www.readbyqxmd.com/read/29022104/deriving-and-understanding-the-risk-of-post-transplant-recurrence-of-nephrotic-syndrome-in-the-light-of-current-molecular-and-genetic-advances
#8
REVIEW
Agnieszka Bierzynska, Moin A Saleem
After renal transplantation, recurrence of the original disease is the second most common cause of graft loss, after rejection. The most dramatic manifestation of this phenomenon is in patients with nephrotic syndrome (NS). NS is a descriptive term describing a clinical picture centred on proteinuria arising from damage to the glomerular filtration barrier (GFB). There are many different drivers of that damage, ranging from immune dysregulation to genetic disorders and chronic disease/infections. The main categories in childhood are "idiopathic" (presumed immune mediated) and genetic NS, with further stratification of the idiopathic group according to steroid responses...
October 11, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29018139/shca-adaptor-protein-promotes-nephrin-endocytosis-and-is-upregulated-in-proteinuric-nephropathies
#9
Claire E Martin, Kelly A Petersen, Lamine Aoudjit, Manali Tilak, Vera Eremina, W Rod Hardy, Susan E Quaggin, Tomoko Takano, Nina Jones
Nephrin is a key structural component of the podocyte slit diaphragm, and proper expression of nephrin on the cell surface is critical to ensure integrity of the blood filtration barrier. Maintenance of nephrin within this unique cell junction has been proposed to require dynamic phosphorylation events and endocytic recycling, although the molecular mechanisms that control this interplay are poorly understood. Here, we investigated the possibility that the phosphotyrosine adaptor protein ShcA regulates nephrin turnover...
October 10, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28993503/myh9-e1841k-mutation-augments-proteinuria-and-podocyte-injury-and-migration
#10
Sylvia Cechova, Fan Dong, Fang Chan, Michael J Kelley, Phillip Ruiz, Thu H Le
Intronic variants of the MYH9 gene that encodes the nonmuscle myosin heavy chain IIA are associated with diabetic nephropathy in European Americans and with sickle cell disease-associated nephropathy. However, the causal functional variants of MYH9 have remained elusive. Rare missense mutations in MYH9 cause macrothrombocytopenia and are occasionally associated with development of nephropathy. The E1841K mutation is among the common MYH9 missense mutations and has been associated with nephropathy in some carriers...
October 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28992221/the-diabetes-pandemic-suggests-unmet-needs-for-ckd-with-diabetes-in-addition-to-diabetic-nephropathy-implications-for-pre-clinical-research-and-drug-testing
#11
Lidia Anguiano Gómez, Yutian Lei, Satish Kumar Devarapu, Hans-Joachim Anders
Curing 'diabetic nephropathy' is considered an unmet medical need of high priority. We propose to question the concept of 'diabetic nephropathy' that implies diabetes as the predominant cause of kidney disease, which may not apply to the majority of type 2 diabetics approaching end-stage kidney disease. With the onset of diabetes, hyperglycaemia/sodium-glucose co-transporter-2-driven glomerular hyperfiltration promotes nephron hypertrophy, which, however, on its own, causes proteinuria not before a decade later, probably because podocyte hypertrophy can usually accommodate an increase in the filtration surface...
July 31, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28992095/the-reduction-of-heparan-sulphate-in-the-glomerular-basement-membrane-does-not-augment-urinary-albumin-excretion
#12
Satoshi Aoki, Akiko Saito-Hakoda, Takeo Yoshikawa, Kyoko Shimizu, Kiyomi Kisu, Susumu Suzuki, Kiyoshi Takagi, Shuji Mizumoto, Shuhei Yamada, Toin H van Kuppevelt, Atsushi Yokoyama, Taiji Matsusaka, Hiroshi Sato, Sadayoshi Ito, Akira Sugawara
Background: Heparan sulphate proteoglycan (HSPG) is present in the glomerular basement membrane (GBM) and is thought to play a major role in the glomerular charge barrier. Reductions and structural alterations of HSPG are observed in different types of kidney diseases accompanied by proteinuria. However, their causal relations remain unknown. Methods: We generated podocyte-specific exostosin-like 3 gene ( Extl3 ) knockout mice ( Extl3KO ) using a Cre-loxP recombination approach...
July 8, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28990091/wwc1-promotes-podocyte-survival-via-stabilizing-slit-diaphragm-protein-dendrin
#13
Ting Lin, Li Zhang, Shuangxin Liu, Yuanhan Chen, Hong Zhang, Xingchen Zhao, Ruizhao Li, Qianmei Zhang, Ruyi Liao, Zongshun Huang, Bin Zhang, Wenjian Wang, Xinling Liang, Wei Shi
Previous studies have indicated that glomerular podocyte injury serves a crucial role in proteinuria during the process of chronic kidney disease. The slit diaphragm of podocytes forms the final barrier to proteinuria. Dendrin, a constituent of the slit diaphragm protein complex, has been observed to relocate from the slit diaphragm to the nuclei in injured podocytes and promote podocyte apoptosis. However, the exact mechanism for nuclear relocation of dendrin remains unclear. The expression of WWC1 in podocyte injury induced by lipopolysaccharides (LPS) or adriamycin (ADR) was detected by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blotting and the immunofluorescence assay...
October 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28987240/protein-tyrosine-phosphatase-1b-deficiency-in-podocytes-mitigates-hyperglycemia-induced-renal-injury
#14
Yoshihiro Ito, Ming-Fo Hsu, Ahmed Bettaieb, Shinichiro Koike, Aline Mello, Miguel Calvo-Rubio, Jose M Villalba, Fawaz G Haj
OBJECTIVE: Diabetic nephropathy is one of the most devastating complications of diabetes, and growing evidence implicates podocyte dysfunction in disease pathogenesis. The objective of this study was to investigate the contribution of protein tyrosine phosphatase 1B (PTP1B) in podocytes to hyperglycemia-induced renal injury. METHODS: To determine the in vivo function of PTP1B in podocytes we generated mice with podocyte-specific PTP1B disruption (hereafter termed pod-PTP1B KO)...
November 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28982981/the-hippo-pathway-regulator-kibra-promotes-podocyte-injury-by-inhibiting-yap-signaling-and-disrupting-actin-cytoskeletal-dynamics
#15
Kristin Meliambro, Jenny S Wong, Justina Ray, Rhodora C Calizo, Sara Towne, Beatriz Cole, Fadi El Salem, Ronald E Gordon, Lewis Kaufman, John C He, Evren U Azeloglu, Kirk N Campbell
Kidney podocytes represent a key constituent of the glomerular filtration barrier. Identifying the molecular mechanisms of podocyte injury and survival is important for better understanding and management of kidney diseases. KIBRA (KIdney BRAin protein), an upstream regulator of the Hippo signaling pathway encoded by the Wwc1 gene, shares the pro-injury properties of its putative binding partner dendrin and antagonizes the pro-survival signaling of the downstream Hippo pathway effector YAP (Yes-associated protein) in Drosophila and MCF10A cells...
October 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28972886/paeoniflorin-ameliorates-adriamycin-induced-nephrotic-syndrome-through-the-ppar%C3%AE-angptl4-pathway-in-vivo-and-vitro
#16
Ruirui Lu, Jie Zhou, Bihao Liu, Ning Liang, Yu He, Lixia Bai, Peichun Zhang, Yanchun Zhong, Yuan Zhou, Jiuyao Zhou
Paeoniflorin (PF), an effective composition that is extracted from Radix Paeoniae Alba, plays a role in protecting against various kidney diseases. However, the mechanism of PF on nephrotic syndrome (NS) remains unclear. The aim of this study was to investigate the protective role of PF on Adriamycin (ADR)-induced NS in vivo and vitro as well as its potential mechanism. In animal study, PF significantly decreased the levels of 24-h urine protein, blood urea nitrogen, serum creatinine, total cholesterol and triglycerides in NS rats, but increased the total protein and albumin levels...
September 30, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28971604/an-integrin-antagonist-mk-0429-decreases-proteinuria-and-renal-fibrosis-in-the-zsf1-rat-diabetic-nephropathy-model
#17
Xiaoyan Zhou, Ji Zhang, Robin Haimbach, Wei Zhu, Rosemary Mayer-Ezell, Margarita Garcia-Calvo, Elizabeth Smith, Olga Price, Yanqing Kan, Emanuel Zycband, Yonghua Zhu, Maarten Hoek, Jason M Cox, Lijun Ma, David E Kelley, Shirly Pinto
Multiple integrins have been implicated in modulating renal function. Modulation of integrin function can lead to pathophysiological processes associated with diabetic nephropathy such as alterations in the glomerular filtration barrier and kidney fibrosis. The complexity of these pathophysiological changes implies that multiple integrin subtypes might need to be targeted to ameliorate the progression of renal disease. To address this hypothesis, we investigated the effects of MK-0429, a compound that was originally developed as an αvβ3 inhibitor for the treatment of osteoporosis, on renal function and fibrosis...
October 2017: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28970584/endoplasmic-reticulum-stress-the-unfolded-protein-response-and-autophagy-in-kidney-diseases
#18
REVIEW
Andrey V Cybulsky
Progress has been made in our understanding of the mechanisms of endoplasmic reticulum (ER) proteostasis, ER stress and the unfolded protein response (UPR), as well as ER stress-induced autophagy, in the kidney. Experimental models have revealed that disruption of the UPR, including a protein that senses misfolded proteins (namely, inositol-requiring enzyme 1α) in mouse podocytes causes podocyte injury and albuminuria as mice age. Protein misfolding and ER stress are evident in various renal diseases, including primary glomerulonephritides, glomerulopathies associated with genetic mutations, diabetic nephropathy, acute kidney injury, chronic kidney disease and renal fibrosis...
November 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28966119/wt1-is-necessary-for-the-proliferation-and-migration-of-cells-of-renin-lineage-following-kidney-podocyte-depletion
#19
Natalya V Kaverina, Diana G Eng, Andrea D Largent, Ilse Daehn, Anthony Chang, Kenneth W Gross, Jeffrey W Pippin, Peter Hohenstein, Stuart J Shankland
Wilms' tumor suppressor 1 (WT1) plays an important role in cell proliferation and mesenchymal-epithelial balance in normal development and disease. Here, we show that following podocyte depletion in three experimental models, and in patients with focal segmental glomerulosclerosis (FSGS) and membranous nephropathy, WT1 increased significantly in cells of renin lineage (CoRL). In an animal model of FSGS in RenWt1(fl/fl) reporter mice with inducible deletion of WT1 in CoRL, CoRL proliferation and migration to the glomerulus was reduced, and glomerular disease was worse compared with wild-type mice...
October 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28963832/-membranous-glomerulonephritis-mgn-ongoing-studies
#20
REVIEW
Gaetano La Manna, Olga Baraldi, Vania Cunia, Valeria Corradetti, Valeria Aiello, Marco Busutti, Lorenzo Gasperoni, Alessandra Spazzoli, Giorgia Comai
The membranous nephropathy (MN) is the major cause of nephrotic syndrome in in the adult, account for 20% of cases with annual incidence is 1 in 100.000. In the past 10 years, the role of podocytes has been identified; environmental triggers in genetically predisposed patients can activate podocytes to exhibit antigenic epitopes (receptor of phospholipase A2, thrombospondin type 1) that become targets of specific autoantibodies with subsequent complement activation. The discovery of this mechanisms has opened new horizons in the therapy of MN and novel drugs are available with more specific mechanism of action...
September 28, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
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