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https://www.readbyqxmd.com/read/29458174/networks-that-link-cytoskeletal-regulators-and-diaphragm-proteins-underpin-filtration-function-in-drosophila-nephrocytes
#1
Simi Muraleedharan, Aksah Sam, Helen Skaer, Maneesha S Inamdar
Insect nephrocytes provide a valuable model for kidney disease, as they are structurally and functionally homologous to mammalian kidney podocytes. They possess an exceptional macromolecular assembly, the nephrocyte diaphragm (ND), which serves as a filtration barrier and helps maintain tissue homeostasis by filtering out wastes and toxic products. However, the elements that maintain nephrocyte architecture and the ND are not understood. We show that Drosophila nephrocytes have a unique cytoplasmic cluster of F-actin, which is maintained by the microtubule cytoskeleton and Rho-GTPases...
February 16, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29455733/taxus-chinensis-ameliorates-diabetic-nephropathy-through-down-regulating-tgf-%C3%AE-1-smad-pathway
#2
Hong-Bo Weng, Wen-Ke Han, Yan-Wen Xiong, Zhou-Hui Jin, Zhen Lan, Cheng Liu, Xue-Mei Zhang, Wen Peng
Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg-1 body weight) intraperitoneally. The rats with blood glucose levels higher than 16...
February 2018: Chinese Journal of Natural Medicines
https://www.readbyqxmd.com/read/29452609/screening-drugs-for-kidney-disease-targeting-the-podocyte
#3
Joshua S Bryer, Katalin Susztak
Podocytes cover the kidney glomerular basement membrane and present the final barrier in the renal filtration system. Podocyte loss, observed in most kidney diseases, correlates with kidney function decline. In this issue of Cell Chemical Biology, Seiber et al. (2018), using a high-throughput chemical screen, identified the compound CDG-0876, which improved podocyte survival.
February 15, 2018: Cell Chemical Biology
https://www.readbyqxmd.com/read/29449955/prospects-for-precision-medicine-in-glomerulonephritis-treatment
#4
REVIEW
Yulu Cherry Liu, Justin Chun
Background: Glomerulonephritis (GN) consists of a group of kidney diseases that are categorized based on shared histopathological features. The current classifications for GN make it difficult to distinguish the individual variability in presentation, disease progression, and response to treatment. GN is a significant cause of end-stage renal disease (ESRD), and improved therapies are desperately needed because current immunosuppressive therapies sometimes lack efficacy and can lead to significant toxicities...
2018: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/29449563/cinacalcet-mediated-activation-of-the-camkk%C3%AE-lkb1-ampk-pathway-attenuates-diabetic-nephropathy-in-db-db-mice-by-modulation-of-apoptosis-and-autophagy
#5
Ji Hee Lim, Hyung Wook Kim, Min Young Kim, Tae Woo Kim, Eun Nim Kim, Yaeni Kim, Sungjin Chung, Young Soo Kim, Bum Soon Choi, Yong-Soo Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Apoptosis and autophagy are harmoniously regulated biological processes for maintaining tissue homeostasis. AMP-activated protein kinase (AMPK) functions as a metabolic sensor to coordinate cellular survival and function in various organs, including the kidney. We investigated the renoprotective effects of cinacalcet in high-glucose treated human glomerular endothelial cells (HGECs), murine podocytes and C57BLKS/J-db/db mice. In cultured HGECs and podocytes, cinacalcet decreased oxidative stress and apoptosis and increased autophagy that were attributed to the increment of intracellular Ca2+ concentration and the phosphorylation of Ca2+ /calmodulin-dependent protein kinase kinaseβ (CaMKKβ)-Liver kinase B1 (LKB1)-AMPK and their downstream signals including the phosphorylation of endothelial nitric oxide synthase (eNOS) and increases in superoxide dismutases and B cell leukemia/lymphoma 2/BCL-2-associated X protein expression...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29448244/mir-499-ameliorates-podocyte-injury-by-targeting-calcineurin-in-minimal-change-disease
#6
Kaiyue Zhang, Wenjuan Sun, Lai Zhang, Xuefang Xu, Jidong Wang, Yan Hong
BACKGROUND: Podocyte injury is a hallmark of minimal change disease (MCD). Calcineurin inhibitors have been widely used in the current treatment of MCD, and miR-499 may target calcineurin. We aimed to study the function of miR-499 in MCD and test whether miR-499 delivery can improve MCD. METHODS: An MCD mouse model was generated using puromycin aminonucleoside (PAN). MiR-499 was delivered using lentiviruses. Biochemical indicators including serum albumin, triglyceride, cholesterol, and 24-h urine protein were determined...
February 15, 2018: American Journal of Nephrology
https://www.readbyqxmd.com/read/29446486/interleukin-17a-participates-in-podocyte-injury-by-inducing-il-1%C3%AE-secretion-through-ros-nlrp3-inflammasome-caspase-1-pathway
#7
Junli Yan, Yao Li, Haiping Yang, Li Zhang, Baohui Yang, Mo Wang, Qiu Li
Studies show that the Th17/IL-17A axis plays an important role in the pathogenesis of kidney diseases. Previously, we also showed that IL-17A may play a role in the pathogenesis of primary nephrotic syndrome; however, the underlying mechanism(s) is unclear. The aim of this study was to explore the molecular mechanism of IL-17A inducing podocyte injury in vitro. In this study, the NLRP3 inflammsome activation and the morphology of podocytes were detected by western blot and immunofluorescence .The results showed that podocytes persistently expressed IL-17A receptor, and that NLRP3 inflammasome in these cells was activated upon exposure to IL-17A...
February 15, 2018: Scandinavian Journal of Immunology
https://www.readbyqxmd.com/read/29446059/the-novel-involvement-of-podocyte-autophagic-activity-in-the-pathogenesis-of-lupus-nephritis
#8
Juan Jin, Meiyu Ye, Li Zhao, Wenli Zou, Wei Shen, Hongjuan Zhang, Jianguang Gong, Qiang He
BACKGROUND: Lupus nephritis (LN) is one of the most common and severe complications in Systemic lupus erythematosus patients, and the mechanism underlining the pathogenesis of LN is still unknown. Autophagy plays vital roles in maintaining cell homeostasis and is involved in the pathogenesis of many diseases. In this study, we investigated the role of autophagy in the progression of LN. METHODS: Autophagic activities in podocytes of both LN patients (Class IV and V) and mice were evaluated...
February 15, 2018: Histology and Histopathology
https://www.readbyqxmd.com/read/29444469/mangiferin-prevents-diabetic-nephropathy-progression-and-protects-podocyte-function-via-autophagy-in-diabetic-rat-glomeruli
#9
Xiaodan Wang, Lihui Gao, Hua Lin, Jingling Song, Jinwen Wang, Yumin Yin, Jianghu Zhao, Xiangwei Xu, Zhenkun Li, Ling Li
Diabetic nephropathy (DN) is one of the most severe microangiopathies of diabetes mellitus and is a leading cause of end stage renal disease. Numerous studies suggest that podocyte injury contributes to progressive proteinuria. Podocytes are highly specialized, terminally differentiated cells that are unable to proliferate, autophagy plays a key role in maintaining the structure and function of podocytes. Autophagy impairment is involved in the pathogenesis of podocyte loss, which leads to massive proteinuria in DN...
February 11, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29439807/could-notch-signaling-pathway-be-a-potential-therapeutic-option-in-renal-diseases
#10
Laura Marquez-Exposito, Elena Cantero-Navarro, Carolina Lavoz, Marta Fierro-Fernández, Jonay Poveda, Sandra Rayego-Mateos, Raúl R Rodrigues-Diez, José Luis Morgado-Pascual, Macarena Orejudo, Sergio Mezzano, Marta Ruiz-Ortega
Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells...
February 10, 2018: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/29436620/highglucose-induces-podocyteepithelial%C3%A2-to%C3%A2-mesenchymal-transition-by-demethylation%C3%A2-mediated-enhancement-of-mmp9-expression
#11
Li Ling, Libo Chen, Changning Zhang, Shuyan Gui, Haiyan Zhao, Zhengzhang Li
Abnormal expression of matrix metalloproteinase 9 (MMP9) is correlated with podocyte epithelial-to---mesenchymal transition (EMT) in diabetic nephropathy (DN). However, the mechanisms underlying this process are not well defined. Site‑specific demethylation may sustain high expression levels of target genes. In the present study, in order to investigate the association between DNA demethylation of MMP9 promoter and podocyte EMT in DN, human podocytes were cultured in high‑glucose (HG) medium and a rat model of DN was established by intraperitoneal injection of streptozotocin (STZ) to determine whether site‑specific demethylation of the MMP9 promoter was involved in regulating podocyte EMT in DN...
February 2, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29436579/long-noncoding-rna-ensrnog00000037522-is-involved-in-the-podocyte-epithelial%C3%A2-mesenchymal-transition-in-diabetic-rats
#12
Li Ling, Zhen Tan, Changning Zhang, Shuyan Gui, Yuanyuan Hu, Libo Chen
Diabetic nephropathy (DN) is one of the most common complications associated with type I and II diabetes mellitus. Long noncoding RNAs (lncRNAs) have been implicated in various physiological and pathological processes, and recent evidence has demonstrated that they are involved in the process of the epithelial‑mesenchymal transition (EMT). In the present study, the potential functions of lncRNA ENSRNOG00000037522 during the EMT process in DN were investigated. The results identified that the level of the lncRNA ENSRNOG00000037522 was significantly increased in kidney tissues collected from rats with streptozocin (STZ)‑induced DN accompanied by impairment of the glomerular podocytes...
February 5, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29435202/podocyte-derived-microparticles-promote-proximal-tubule-fibrotic-signaling-via-p38-mapk-and-cd36
#13
Mercedes N Munkonda, Shareef Akbari, Chloe Landry, Suzy Sun, Fengxia Xiao, Maddison Turner, Chet E Holterman, Rania Nasrallah, Richard L Hébert, Christopher R J Kennedy, Dylan Burger
Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100-1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses...
2018: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/29434805/overexpression-of-heart-type-fatty-acid-binding-protein-enhances-fatty-acid-induced-podocyte-injury
#14
Qing Gao, Alhossain Sarkar, Yizhi Chen, Bo Xu, Xiaojuan Zhu, Yang Yuan, Tianjun Guan
Deregulated lipid metabolism is a characteristic of metabolic diseases including type 2 diabetes and obesity, and likely contributes to podocyte injury and end-stage kidney disease. Heart-type fatty acid binding protein (H-FABP) was reported to be associated with lipid metabolism. The present study investigated whether H-FABP contributes to podocyte homeostasis. Podocytes were transfected by lentiviral vector to construct a cell line which stably overexpressed H-FABP. Small interfering RNA capable of effectively silencing H-FABP was introduced into podocytes to construct a cell line with H-FABP knockdown...
February 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29434693/overexpression-of-mir-130a-3p-301a-3p-attenuates-high-glucose-induced-mpc5-podocyte-dysfunction-through-suppression-of-tnf-%C3%AE-signaling
#15
Yan Jiang, Wei Wang, Zong-Yang Liu, Yi Xie, Yuan Qian, Xue-Ni Cai
Tumor necrosis factor (TNF)-α has been reported to be important in glomerulonephritis, which is closely associated with podocyte dysfunction and apoptosis. However, the precise mechanisms by which TNF-α expression are regulated remain unclear. The purpose of the present study was to investigate the role of microRNA (miR)-130a-3p/301a-3p in the post-transcriptional control of TNF-α expression and high glucose (HG)-induced podocyte dysfunction. Mice MPC5 podocytes were incubated with HG and transfected with miR-130a-3p/301a-3p mimics or inhibitors, reactive oxygen species (ROS) levels were measured by flow cytometry assay, and the mRNA and protein levels were assayed by using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively...
January 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29432216/glomerulogenesis-and-the-role-of-endothelium
#16
Michio Nagata
PURPOSE OF REVIEW: Earlier works of the glomerulogenesis described morphological steps and protein expression during in-vivo and in-vitro kidney development. Recent technologies using cell-specific or conditional knock-out mice for several factors provide important knowledge about cross-talk signaling among resident cells as local events. Based on the recent advancement, this review revisits comprehensive morphological development of the glomerulus. RECENT FINDINGS: Interactions of presumptive podocyte vascular endothelial growth factor with vascular endothelial growth factor-2 on angioblasts initiate glomerular vascularization...
February 9, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29429961/generation-of-functioning-nephrons-by-implanting-human-pluripotent-stem-cell-derived-kidney-progenitors
#17
Ioannis Bantounas, Parisa Ranjzad, Faris Tengku, Edina Silajdžić, Duncan Forster, Marie-Claude Asselin, Philip Lewis, Rachel Lennon, Antonius Plagge, Qi Wang, Adrian S Woolf, Susan J Kimber
Human pluripotent stem cells (hPSCs) hold great promise for understanding kidney development and disease. We reproducibly differentiated three genetically distinct wild-type hPSC lines to kidney precursors that underwent rudimentary morphogenesis in vitro. They expressed nephron and collecting duct lineage marker genes, several of which are mutated in human kidney disease. Lentiviral-transduced hPSCs expressing reporter genes differentiated similarly to controls in vitro. Kidney progenitors were subcutaneously implanted into immunodeficient mice...
February 7, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29428904/developmental-disorder-of-podocytes-and-the-related-renal-diseases
#18
Ya-Nan Zhu, Ying Ao, Bin Li, Yang Wan, Hui Wang
Podocyte is one of the main components of glomerular filtration barrier in the kidney; the loss or dysfunction of podocyte could impair the functions of glomerular filtration barrier, leading to development of various renal diseases. Podocyte is a terminally differentiated cell, and thus does not possess any proliferative properties. Accordingly, its number and contribution to renal function are initially determined by its normal development. Information from the literature and results of our research indicate that genetic factors or prenatal adverse environment could cause developmental retardation of podocytes, thereby suggesting the potential fetal developmental origin(s) of kidney diseases, and involvement of epigenetic mechanisms in the regulation of key genes in podocyte development...
February 20, 2018: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/29422652/rage-aptamer-attenuates-deoxycorticosterone-acetate-salt-induced-renal-injury-in-mice
#19
Kensei Taguchi, Sho-Ichi Yamagishi, Miyuki Yokoro, Sakuya Ito, Goh Kodama, Yusuke Kaida, Yosuke Nakayama, Ryotaro Ando, Nana Yamada-Obara, Katsuhiko Asanuma, Takanori Matsui, Yuichiro Higashimoto, Craig R Brooks, Seiji Ueda, Seiya Okuda, Kei Fukami
The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE-RAGE axis and MR system in kidney derangement remains unclear. We screened DNA-aptamer directed against RAGE (RAGE-apt) in vitro and examined its effects on renal injury in uninephrectomized deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mice...
February 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29421811/swiprosin-1-promotes-mitochondria-dependent-apoptosis-of-glomerular-podocytes-via-p38-mapk-pathway-in-early-stage-diabetic-nephropathy
#20
Rong-Mei Wang, Zhi-Bin Wang, Yue Wang, Wei-Ye Liu, Ya Li, Ling-Chang Tong, Su Zhang, Ding-Feng Su, Yong-Bing Cao, Ling Li, Li-Chao Zhang
BACKGROUND/AIMS: Podocyte injury, especially podocyte apoptosis, plays a major role in early-stage diabetic nephropathy (DN). Swiprosin-1, also known as EF hand domain containing 2 (EFhd2), is a Ca2+-binding protein in different cell types. However, the function of swiprosin-1 in podocytes remains unknown. METHODS: The expression and distribution of swiprosin-1 were investigated in the mouse renal glomerulus and conditionally immortalized mouse podocyte cell line MPC-5...
February 2, 2018: Cellular Physiology and Biochemistry
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