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https://www.readbyqxmd.com/read/29050010/calcium-sensing-receptor-stimulation-in-cultured-glomerular-podocytes-induces-trpc6-dependent-calcium-entry-and-rhoa-activation
#1
Lei Zhang, Tianrong Ji, Qin Wang, Kexin Meng, Rui Zhang, He Yang, Chang Liao, Linlin Ma, Jundong Jiao
BACKGROUND/AIMS: Recent studies provided compelling evidence that stimulation of the calcium sensing receptor (CaSR) exerts direct renoprotective action at the glomerular podocyte level. This protective action may be attributed to the RhoA-dependent stabilization of the actin cytoskeleton. However, the underlying mechanisms remain unclear. METHODS: In the present study, an immortalized human podocyte cell line was used. Fluo-3 fluorescence was utilized to determine intracellular Ca2+ concentration ([Ca2+]i), and western blotting was used to measure canonical transient receptor potential 6 (TRPC6) protein expression and RhoA activity...
October 19, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29049388/an-inducible-mouse-model-of-podocin-mutation-related-nephrotic-syndrome
#2
Mansoureh Tabatabaeifar, Tanja Wlodkowski, Ivana Simic, Helga Denc, Geraldine Mollet, Stefanie Weber, John Julius Moyers, Barbara Brühl, Michael Joseph Randles, Rachel Lennon, Corinne Antignac, Franz Schaefer
Mutations in the NPHS2 gene, encoding podocin, cause hereditary nephrotic syndrome. The most common podocin mutation, R138Q, is associated with early disease onset and rapid progression to end-stage renal disease. Knock-in mice carrying a R140Q mutation, the mouse analogue of human R138Q, show developmental arrest of podocytes and lethal renal failure at neonatal age. Here we created a conditional podocin knock-in model named NPHS2 R140Q/-, using a tamoxifen-inducible Cre recombinase, which permits to study the effects of the mutation in postnatal life...
2017: PloS One
https://www.readbyqxmd.com/read/29046486/synaptopodin-is-upregulated-by-il-13-in-eosinophilic-esophagitis-and-regulates-esophageal-epithelial-cell-motility-and-barrier-integrity
#3
Mark Rochman, Jared Travers, J Pablo Abonia, Julie M Caldwell, Marc E Rothenberg
Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus mediated by an IL-13-driven epithelial cell transcriptional program. Herein, we show that the cytoskeletal protein synaptopodin (SYNPO), previously associated with podocytes, is constitutively expressed in esophageal epithelium and induced during allergic inflammation. In addition, we show that the SYNPO gene is transcriptionally and epigenetically regulated by IL-13 in esophageal epithelial cells. SYNPO was expressed in the basal layer of homeostatic esophageal epithelium, colocalized with actin filaments, and expanded into the suprabasal epithelium in EoE patients, where expression was elevated 25-fold compared with control individuals...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29046299/high-content-screening-assay-based-discovery-of-paullones-as-novel-podocyte-protective-agents
#4
Ha Won Lee, Ehtesham Arif, Mehmet Mete Altintas, Kevin Quick, Shrey Maheshwari, Alexandra Plezia, Aqsa Mahmood, Jochen Reiser, Deepak Nihalani, Vineet Gupta
Podocyte dysfunction and loss is an early event and a hallmark of proteinuric kidney diseases. Podocyte's normal function is maintained via its unique cellular architecture that relies on an intracellular network of filaments, including filamentous actin (F-actin) and microtubules, that provides mechanical support. Damage to this filamentous network leads to changes in cellular morphology and results in podocyte injury, dysfunction, and death. Conversely, stabilization of this network protects podocytes and ameliorates proteinuria...
October 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29038896/inducible-atf3-nfat-axis-aggravates-podocyte-injury
#5
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
#6
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
#7
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/29038164/pka-creb-signaling-prevents-adriamycin-induced-podocyte-apoptosis-via-upregulation-of-mitochondrial-respiratory-chain-complexes
#8
Kewei Xie, Mingli Zhu, Peng Xiang, Xiaohuan Chen, Ayijiaken Kasimumali, Renhua Lu, Qin Wang, Shan Mou, Zhaohui Ni, Leyi Gu, Huihua Pang
Previous work showed that the activation of protein kinase A (PKA) signaling promoted mitochondrial fusion and prevented podocyte apoptosis. The cAMP response element binding protein (CREB) is the main downstream transcription factor of PKA signaling. Herein, we show that the pKA-agonist pCPT-cAMP prevented the production of adriamycin (ADR)-induced reactive oxygen species and apoptosis in podocytes, which were inhibited by CREB RNAi. The activation of PKA enhanced mitochondrial function and prevented the ADR-induced decrease of mitochondrial respiratory chain complex I subunits, NADH-ubiquinone oxidoreductase complex (ND) 1/3/4 genes, and protein expression...
October 16, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29035194/clinicopathologic-characteristics-of-light-chain-proximal-tubulopathy-with-light-chain-inclusions-involving-multiple-renal-cell-types%C3%A2
#9
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
#10
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
#11
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/29032153/metformin-overcomes-high-glucose-induced-insulin-resistance-of-podocytes-by-pleiotropic-effects-on-sirt1-and-ampk
#12
Dorota Rogacka, Irena Audzeyenka, Michał Rychłowski, Patrycja Rachubik, Maria Szrejder, Stefan Angielski, Agnieszka Piwkowska
Podocyte insulin sensitivity is critical for glomerular function, and the loss of appropriate insulin signaling leads to alterations and disorders featuring diabetic nephropathy. Energy-sensing pathways, such as AMP-dependent protein kinase (AMPK) and protein deacetylase SIRT1, have been shown to play an important role in insulin resistance. The absence of a stimulating effect of insulin on glucose uptake into podocytes after exposure to hyperglycemic conditions has been demonstrated to be related to a decreased level and activity of SIRT1 protein, leading to reduced AMPK phosphorylation...
October 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29026873/graft-growth-and-podocyte-dedifferentiation-in-donor-recipient-size-mismatch-kidney-transplants
#13
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/29022109/interaction-of-cd80-with-neph1-a-potential-mechanism-of-podocyte-injury
#14
Bhavya Khullar, Renu Balyan, Neelam Oswal, Nidhi Jain, Amita Sharma, Malik Z Abdin, Arvind Bagga, Shinjini Bhatnagar, Nitya Wadhwa, Uma Chandra Mouli Natchu, Anna George, Satyajit Rath, Vineeta Bal, Shailaja Sopory
BACKGROUND: The induction of CD80 on podocytes has been shown in animal models of podocyte injury and in certain cases of nephrotic syndrome. In a lipopolysaccharide (LPS)-induced mouse model of albuminuria, we have recently shown a signalling axis of LPS-myeloid cell activation-TNFα production-podocyte CD80 induction-albuminuria. Therefore, in this report, we investigated the cellular and molecular consequences of TNFα addition and CD80 expression on cultured podocytes. METHODS: A murine podocyte cell line was used for TNFα treatment and for over-expressing CD80...
October 11, 2017: Clinical and Experimental Nephrology
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
#15
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/29021382/sustained-activation-of-guanylate-cyclase-a-with-tdt-a-natriuretic-peptide-derivative-exhibits-cardiorenal-protection-in-dahl-salt-sensitive-hypertensive-rats
#16
Shohei Oishi, Naoko Suzuki, Yuri Hasui, Tsuyoshi Homma, Masanori Obana, Takahiro Nagayama, Yasushi Fujio
Heart failure often presents with prognosis-relevant impaired renal function. To investigate whether the chronic activation of guanylate cyclase-A (GC-A) protects both heart and kidney, we examined the effects of TDT, a neprilysin (NEP)-resistant natriuretic peptide (NP) derivative, on cardiac and renal dysfunction in Dahl salt-sensitive hypertensive rats (DS rats). Pretreatment with NEP or NEP inhibitor did not influence GC-A activation by TDT both in vitro and in vivo, resulting in a long-acting profile of TDT compared to native human atrial NP (hANP)...
October 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29018139/shca-adaptor-protein-promotes-nephrin-endocytosis-and-is-upregulated-in-proteinuric-nephropathies
#17
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
#18
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
#19
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
#20
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
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