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https://www.readbyqxmd.com/read/28535513/pkc-%C3%AE-triggers-egfr-ubiquitination-endocytosis-and-erk-activation-in-podocytes-stimulated-with-high-glucose
#1
Chun-Tao Lei, Yan-Hong Wei, Hui Tang, Qian Wen, Chen Ye, Chun Zhang, Hua Su
BACKGROUND: Protein Kinase C-α (PKC-α) and epidermal growth factor receptor (EGFR) are both involved in diabetic kidney disease; however, the connection between these two proteins during high glucose-induced podocyte injury remains uncertain. METHODS: Diabetes was induced in SD rats by streptozotocin (STZ). Fourteen days later, the kidney cortex was removed and subjected to plasma membrane isolation and lipid raft fractionation. In vitro study human podocyte cell line was differentiated and subjected to various treatments...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28534128/cathepsin-l-activity-correlates-with-proteinuria-in-chronic-kidney-disease-in-humans
#2
Yu Cao, Xing Liu, Ying Li, Yao Lu, Hua Zhong, Weihong Jiang, Alex F Chen, Timothy R Billiar, Hong Yuan, Jingjing Cai
BACKGROUND: The presence and severity of proteinuria is considered an important prognostic marker in patients with chronic kidney disease (CKD) and is associated with mortality and morbidity. Cathepsin L is highly expressed in the foot processes of podocytes in the kidney, which serves as an ultrafiltration barrier. Cathepsin L is also up-regulated in the setting of inflammation as a feature of CKD. Therefore, we postulated that proteinuria severity in CKD patients might correlate with increased serum levels of cathepsin L...
May 22, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28532817/-pro-renin-receptor-as-a-therapeutic-target-for-the-treatment-of-cardiovascular-diseases
#3
REVIEW
Yuan Sun, A H Jan Danser, Xifeng Lu
The discovery of the (pro)renin receptor [(P)RR] 15years ago stimulated ideas on prorenin being more than renin's inactive precursor. Indeed, binding of prorenin to the (P)RR induces a conformational change in the prorenin molecule, allowing it to display angiotensin-generating activity, and additionally results in intracellular signaling in an angiotensin-independent manner. However, the prorenin levels required to observe these angiotensin-dependent and -independent effects of the (P)RR are many orders above its in vivo concentrations, both under normal and pathological conditions...
May 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28528353/adrenomedullin-ameliorates-podocyte-injury-induced-by-puromycin-aminonucleoside-in-vitro-and-in-vivo-through-modulation-of-rho-gtpases
#4
Nan Dong, Lixia Meng, Ruqun Xue, Meng Yu, Zhonghua Zhao, Xueguang Liu
PURPOSE: Podocyte injury is a key event in proteinuric kidney disease and eventually glomerular scarring. While adrenomedullin (AM), a potent vasodilatory peptide, has been reported to confer renoprotection in several experimental models of kidney diseases, its effect on injured podocytes and the related mechanism is still largely unknown. METHODS: Employing Western blotting analysis, immunoprecipitation and immunofluorescence, we investigated the effects of AM on the expressions of podocyte cytoskeletal proteins and Rho-family small GTPases (Rho GTPases) in puromycin aminonucleoside (PAN)-induced podocyte injury, both in cultured podocytes and in PAN nephrosis rats...
May 20, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28523190/expression-of-upar-in-urinary-podocytes-of-patients-with-fabry-disease
#5
Hernán Trimarchi, Romina Canzonieri, Amalia Schiel, Juan Politei, Cristian Costales-Collaguazo, Aníbal Stern, Matías Paulero, Tatiana Rengel, Lara Valiño-Rivas, Mariano Forrester, Fernando Lombi, Vanesa Pomeranz, Romina Iriarte, Alexis Muryan, Alberto Ortiz, María Dolores Sanchez-Niño, Elsa Zotta
Background. Despite enzyme replacement therapy, Fabry nephropathy still progresses. Podocyturia is an irreversible event that antedates proteinuria and leads to chronic renal failure. We evaluated a potential mechanism of podocyte detachment via the expression of the urokinase-type Plasminogen Activator Receptor (uPAR) in urinary podocytes of Fabry patients. Methods. This is a cross-sectional study that included controls (n = 20) and Fabry patients (n = 44) either untreated (n = 23) or treated with agalsidase-β (n = 21)...
2017: International Journal of Nephrology
https://www.readbyqxmd.com/read/28516997/peptide-and-antibody-ligands-for-renal-targeting-nanomedicine-strategies-for-kidney-disease
#6
Jonathan Wang, Jacqueline J Masehi-Lano, Eun Ji Chung
The kidney is one of the body's main filtration organs, and hence, opportunity exists for designing nanomedicine that can naturally accumulate in the kidneys for renal diseases. In addition to traditional physiochemical properties for kidney accumulation, such as size and charge, synthesized nanoparticles can be conjugated with targeting ligands which further home the nanocarriers to cell types of interest. In this review, we highlight key studies that have shown success in utilizing peptide- or antibody-based ligands in nanoparticles to target the glomerulus, podocytes, or renal tubule cells in the kidney...
May 18, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28512641/podocyte-autophagy-a-potential-therapeutic-target-to-prevent-the-progression-of-diabetic-nephropathy
#7
REVIEW
Na Liu, Liuqing Xu, Yingfeng Shi, Shougang Zhuang
Diabetic nephropathy (DN), a leading cause of end-stage renal disease (ESRD), becomes a worldwide problem. Ultrastructural changes of the glomerular filtration barrier, especially the pathological changes of podocytes, lead to proteinuria in patients with diabetes. Podocytes are major components of glomerular filtration barrier, lining outside of the glomerular basement membrane (GBM) to maintain the permeability of the GBM. Autophagy is a high conserved cellular process in lysosomes including impaired protein, cell organelles, and other contents in the cytoplasm...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/28509120/complex-glomerular-pathology-of-thrombotic-microangiopathy-and-focal-segmental-glomerulosclerosis-forms-tumor-like-mass-in-a-renal-transplant-donor-with-severe-renovascular-hypertension
#8
Michio Nagata, Yutaka Yamaguchi, Daisuke Toki, Izumi Yamamoto, Hiroaki Shinmura, Hiroshi Kawaguchi
The pathogenesis of glomerular hypertension-mediated FSGS and its histological variations in humans remains unknown. A 47-year-old man developed nephrotic syndrome, renal dysfunction, and malignant hypertension 2 years after donating a kidney to his son. The donor's remnant kidney developed renal mass at an upper pole which was fed by an aberrant artery that branched from the root of the renal artery. Furthermore, the main non-aberrant renal artery demonstrated severe stenosis that caused renovascular hypertension, resulting in malignant hypertension...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28508947/podocytes-from-the-diagnostic-and-therapeutic-point-of-view
#9
REVIEW
Janina Müller-Deile, Mario Schiffer
The central role of podocytes in glomerular diseases makes this cell type an interesting diagnostic tool as well as a therapeutic target. In this review, we discuss the current literature on the use of podocytes and podocyte-specific markers as non-invasive diagnostic tools in different glomerulopathies. Furthermore, we highlight the direct effects of drugs currently used to treat primary glomerular diseases and describe their direct cellular effects on podocytes. A new therapeutic potential is seen in drugs targeting the podocytic actin cytoskeleton which is essential for podocyte foot process structure and function...
May 16, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28505239/foxo1-promotes-mitophagy-in-the-podocytes-of-diabetic-male-mice-via-the-pink1-parkin-pathway
#10
Wen Li, Mengmeng Du, Qingzhu Wang, Xiaojun Ma, Lina Wu, Feng Guo, Hongfei Ji, Fengjuan Huang, Guijun Qin
We recently showed that Forkhead-box class O1 (FoxO1) activation protects against high glucose-induced injury by preventing mitochondrial dysfunction in the rat kidney cortex. In addition, FoxO1 has been reported to mediate PINK1 transcription and promote autophagy in response to mitochondrial oxidative stress in murine cardiomyocytes. In this study, we ascertained whether over-expressing FoxO1 in the kidney cortex reverses pre-established diabetic nephropathy in animal models. The effect of FoxO1 on mitophagy signaling pathways was evaluated in mouse podocytes...
May 12, 2017: Endocrinology
https://www.readbyqxmd.com/read/28502979/chrysin-ameliorates-podocyte-injury-and-slit-diaphragm-protein-loss-via-inhibition-of-the-perk-eif2%C3%AE-atf-chop-pathway-in-diabetic-mice
#11
Min-Kyung Kang, Sin-Hye Park, Yun-Ho Kim, Eun-Jung Lee, Lucia Dwi Antika, Dong Yeon Kim, Yean-Jung Choi, Young-Hee Kang
Glomerular epithelial podocytes are highly specialized cells that play a crucial role in maintaining normal function of the glomerular filtration barrier via their foot processes. Chrysin (5,7-dihydroxyflavone) is a natural flavonoid found in propolis and mushrooms that has anti-inflammatory, antioxidant and anticancer properties. This study aimed to evaluate the renoprotective effects of chrysin on podocyte apoptotic loss and slit diaphragm protein deficiency in high glucose-exposed podocytes and in db/db mouse kidneys...
May 15, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28501303/potential-relevance-of-shear-stress-for-slit-diaphragm-and-podocyte-function
#12
Wilhelm Kriz, Kevin V Lemley
Filtrate flow through the glomerular barrier produces shear stresses that tend to disconnect podocytes from the glomerular basement membrane. Forces are highest within the filtration slits. The slit diaphragm mechanically balances the lateral components of the shear stresses on opposing foot processes, preventing widening of the slit.
June 2017: Kidney International
https://www.readbyqxmd.com/read/28501082/a-high-content-screening-technology-for-quantitatively-studying-podocyte-dynamics
#13
REVIEW
Jochen Reiser, Ha Won Lee, Vineet Gupta, Mehmet M Altintas
Podocytes form the visceral layer of a kidney glomerulus and express a characteristic octopus-like cellular architecture specialized for the ultrafiltration of blood. The cytoskeletal dynamics and structural elasticity of podocytes rely on the self-organization of highly interconnected actin bundles, and the maintenance of these features is important for the intact glomerular filtration. Development of more differentiated podocytes in culture has dramatically increased our understanding of the molecular mechanisms regulating podocyte actin dynamics...
May 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28498096/characterization-of-the-anti-bovine-podoplanin-monoclonal-antibody-pmab-44
#14
Shinji Yamada, Ryusuke Honma, Mika K Kaneko, Takuro Nakamura, Miyuki Yanaka, Noriko Saidoh, Michiaki Takagi, Satoru Konnai, Yukinari Kato
A type I transmembrane sialoglycoprotein podoplanin (PDPN) is expressed in several normal cells, including podocytes of the kidney, type I alveolar cells of the lung, and lymphatic endothelial cells. We recently produced an anti-bovine PDPN (bovPDPN) monoclonal antibody (mAb), PMab-44, by immunizing mice with recombinant proteins of bovPDPN. In this study, we determined the critical epitope of PMab-44 for the recognition of bovPDPN using many deletion mutants and point mutants of bovPDPN. Flow cytometric analyses revealed that the epitope of PMab-44 was Glu46-Thr50, which corresponds to platelet aggregation-stimulating (PLAG) domain-3...
May 12, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28497421/decreased-mir-128-and-increased-mir-21-synergistically-cause-podocyte-injury-in-sepsis
#15
Shanshan Wang, Jun Wang, Zengdi Zhang, Hongjun Miao
OBJECTIVE: Glomerular podocytes are injured in sepsis. We studied, in a sepsis patient, whether microRNAs (miRNAs) play a role in the podocyte injury. METHODS: Podocytes were cultured and treated with lipopolysaccharide (LPS). Filtration barrier function of podocyte was analyzed with albumin influx assay. Nephrin level was analyzed with reverse transcription polymerase chain reaction (RT-PCR) and western blot. MiRNAs were detected using miRNAs PCR Array and in situ hybridization...
May 11, 2017: Journal of Nephrology
https://www.readbyqxmd.com/read/28491859/autophagy-in-kidney-transplants-of-sirolimus-treated-recipients
#16
Sagar Bhayana, Arpita Baisantry, Thomas D Kraemer, Christoph Wrede, Jan Hegermann, Jan-Hinrich Bräsen, Clemens Bockmeyer, Jan Ulrich Becker, Matthias Ochs, Wilfried Gwinner, Hermann Haller, Anette Melk, Roland Schmitt
BACKGROUND: Mammalian target of rapamycin (mTOR) inhibitors are increasingly used as immunosuppressive agents in kidney transplantation. In the experimental setting it has been shown that mTOR inhibitors promote autophagy, but the concept that this might also occur in transplant patients has not been addressed. OBJECTIVES: This study was designed to investigate the association between mTOR inhibition and autophagy in renal transplants under routine clinical conditions...
March 2017: Journal of Nephropathology
https://www.readbyqxmd.com/read/28491286/unwinding-focal-segmental-glomerulosclerosis
#17
REVIEW
Vasil Peev, Eunsil Hahm, Jochen Reiser
Focal segmental glomerulosclerosis (FSGS) represents the most common primary glomerular disease responsible for the development of end-stage renal disease (ESRD) in the United States (US). The disease progresses from podocyte injury to chronic kidney disease (CKD), ultimately leading to total nephron degeneration. Extensive basic science research has been conducted to unwind the mechanisms of FSGS and, with those insights, understand major contributors of CKD in general. As a result, several putative molecules and pathways have been studied, all implicated in the disease; some serve, in addition, as early biomarkers...
2017: F1000Research
https://www.readbyqxmd.com/read/28490532/podocyte-specific-knockout-ko-of-cyclooxygenase-2-cox2-exacerbates-diabetic-kidney-disease
#18
Limng Wang, Yonggang Sha, Jingyi Bai, William Eisner, Mathew A Sparks, Anne F Buckley, Robert F Spurney
Enhanced expression of cyclooxygenase 2 (COX2) in podocytes contributes to glomerular injury in diabetic kidney disease, but some basal level of podocyte COX2 expression might be required to promote podocyte attachment and/or survival. To investigate the role of podocyte COX2 expression in diabetic kidney disease, we deleted COX2 specifically in podocytes in a mouse model of type 1 diabetes mellitus (Akita mice). Podocyte specific knockout (KO) of COX2 did not affect renal morphology or albuminuria in non-diabetic mice...
May 10, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28488220/pla2r-positive-primary-membranous-nephropathy-in-a-child-with-ipex-syndrome
#19
Teresa Chuva, Frederick Pfister, Ortraud Beringer, Kerstin Felgentreff, Maike Büttner-Herold, Kerstin Amann
BACKGROUND: Immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare primary immunodeficiency syndrome characterized by the development of multiple autoimmune disorders in affected individuals. Different forms of renal injury have been reported in IPEX syndrome, and membranous nephropathy (MN) is among the most common glomerulopathies found. However, the exact pathogenesis of MN in this setting has not been elucidated, and it is not clear whether it is part of the clinical spectrum of the disease or secondary to medications, infections or other concomitant insults...
May 9, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28485854/podocyte-specific-soluble-epoxide-hydrolase-deficiency-in-mice-attenuates-acute-kidney-injury
#20
Ahmed Bettaieb, Shinichiro Koike, Samah Chahed, Yi Zhao, Santana Bachaalany, Nader Hashoush, James Graham, Fatima Huma, Peter J Havel, Artiom Gruzdev, Darryl C Zeldin, Bruce D Hammock, Fawaz G Haj
Podocytes play an important role in maintaining glomerular function, and podocyte injury is a significant component in the pathogenesis of proteinuria. Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose genetic deficiency and pharmacological inhibition have beneficial effects on renal function, but its role in podocytes remains unexplored. The objective of this study was to investigate the contribution of sEH in podocytes to lipopolysaccharide (LPS)-induced kidney injury. We report increased sEH transcript and protein expression in murine podocytes upon LPS challenge...
May 9, 2017: FEBS Journal
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