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https://www.readbyqxmd.com/read/28339909/il-17-and-cd40-ligand-synergistically-stimulate-the-chronicity-of-diabetic-nephropathy
#1
Huey-Liang Kuo, Chiu-Ching Huang, Tze-Yi Lin, Ching-Yuang Lin
Background.: Early stages of diabetic nephropathy (DN) are characterized by an influx of inflammatory cells. Interactions between infiltrating T cells and podocytes may play an important role in the ongoing inflammatory response and remodelling. The aim of this study was to explore the role of IL-17 and CD40 ligand (CD40L) in DN. Methods.: The study design involved a case series. Kidney biopsy samples of 69 patients with type 2 diabetes were assessed for the presence of CD4 +  IL-17 +  T cells...
March 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339907/o-linked-%C3%AE-n-acetylglucosamine-modification-of-proteins-is-essential-for-foot-process-maturation-and-survival-in-podocytes
#2
Shinya Ono, Shinji Kume, Mako Yasuda-Yamahara, Kosuke Yamahara, Naoko Takeda, Masami Chin-Kanasaki, Hisazumi Araki, Osamu Sekine, Hideki Yokoi, Masashi Mukoyama, Takashi Uzu, Shin-Ichi Araki, Hiroshi Maegawa
Background.: O-linked β- N -acetylglucosamine modification O-GlcNAcylation) is a post-translational modification of intracellular proteins, serving as a nutrient sensor. Growing evidence has demonstrated its physiological and pathological importance in various mammalian tissues. This study examined the physiological role of O-GlcNAcylation in podocyte function and development. Methods.: O-GlcNAc transferase (Ogt) is a critical enzyme for O-GlcNAcylation and resides on the X chromosome...
February 27, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339567/role-of-biomechanical-forces-in-hyperfiltration-mediated-glomerular-injury-in-congenital-anomalies-of-the-kidney-and-urinary-tract
#3
Tarak Srivastava, Ganesh Thiagarajan, Uri S Alon, Ram Sharma, Ashraf El-Meanawy, Ellen T McCarthy, Virginia J Savin, Mukut Sharma
Congenital anomalies of the kidney and urinary tract (CAKUT) including solitary kidney constitute the main cause of progressive chronic kidney disease (CKD) in children. Children born with CAKUT develop signs of CKD only during adolescence and do not respond to renin-angiotensin-aldosterone system blockers. Early cellular changes underlying CKD progression to end-stage renal disease by early adulthood are not well understood. The mechanism of maladaptive hyperfiltration that occurs from loss of functional nephrons, including solitary kidney, is not clear...
January 17, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28339051/protective-effects-of-tacrolimus-on-podocytes-in-early-diabetic-nephropathy-in-rats
#4
Tao Peng, Xiangdi Chang, Jie Wang, Junhui Zhen, Xiangdong Yang, Zhao Hu
The aim of the present study was to investigate the protective effect of tacrolimus on early podocyte damage in rats with diabetic nephropathy (DN). A total of 38 normal male Sprague‑Dawley rats were randomly divided into four groups: Normal control group (group N; n=8), DN group (n=10), tacrolimus (FK506) treatment group (group F; n=10), benazepril (Lotensin) treatment group (group L; n=10). The rats in groups DN, F and L were administered with streptozotocin (STZ; 60 mg/kg) by intraperitoneal injection to establish the diabetic rat model...
March 22, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28337255/combined-therapy-with-melatonin-and-exendin-4-effectively-attenuated-the-deterioration-of-renal-function-in-rat-cardiorenal-syndrome
#5
Kuan-Hung Chen, Chih-Hung Chen, Christopher Glenn Wallace, Yen-Ta Chen, Chih-Chao Yang, Pei-Hsun Sung, Hsin-Ju Chiang, Yi-Ling Chen, Sarah Chua, Hon-Kan Yip, Jiin-Tsuey Cheng
This study tested the hypothesis that combined therapy with melatonin (Mel) and exendin-4 (Ex4) would be superior to either therapy alone for preventing the deterioration of renal function in cardiorenal syndrome (CRS). Male adult Sprague Dawley rats (n = 48) were randomly and equally divided into sham-control (SC), chronic kidney disease (CKD; induced by 5/6 nephrectomy), CRS (CKD + dilated cardiomyopathy, DCM; induced by doxorubicin 7 mg/kg i.p. every 5 days, 4 doses), CRS-Mel (20 mg/kg/day), CRS-Ex4 (10 µg/kg/day) and CRS-Mel-Ex4...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28337250/podocyte-injury-and-albuminuria-in-experimental-hyperuricemic-model-rats
#6
Shinichiro Asakawa, Shigeru Shibata, Chikayuki Morimoto, Takeshi Shiraishi, Takashi Nakamura, Yoshifuru Tamura, Takanori Kumagai, Makoto Hosoyamada, Shunya Uchida
Although hyperuricemia is shown to accelerate chronic kidney disease, the mechanisms remain unclear. Accumulating studies also indicate that uric acid has both pro- and antioxidant properties. We postulated that hyperuricemia impairs the function of glomerular podocytes, resulting in albuminuria. Hyperuricemic model was induced by oral administration of 2% oxonic acid, a uricase inhibitor. Oxonic acid caused a twofold increase in serum uric acid levels at 8 weeks when compared to control animals. Hyperuricemia in this model was associated with the increase in blood pressure and the wall-thickening of afferent arterioles as well as arcuate arteries...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28336924/rtn1a-mediated-endoplasmic-reticulum-stress-in-podocyte-injury-and-diabetic-nephropathy
#7
Ying Fan, Jing Zhang, Wenzhen Xiao, Kyung Lee, Zhengzhe Li, Jiejun Wen, Li He, Dingkun Gui, Rui Xue, Guihua Jian, Xiaohua Sheng, John Cijiang He, Niansong Wang
We previously reported a critical role of reticulon (RTN) 1A in mediating endoplasmic reticulum (ER) stress in kidney tubular cells and the expression of RTN1A correlates with the renal function and the severity of kidney injury in patients with diabetic nephropathy (DN). Here, we determined the roles of RTN1A and ER stress in podocyte injury and DN. We used db/db mice with early unilateral nephrectomy (Unx) as a murine model of progressive DN and treated mice with tauroursodeoxycholic acid (TUDCA), a specific inhibitor of ER stress...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28334007/a-functional-variant-in-neph3-gene-confers-high-risk-of-renal-failure-in-primary-hematuric-glomerulopathies-evidence-for-predisposition-to-microalbuminuria-in-the-general-population
#8
Konstantinos Voskarides, Charalambos Stefanou, Myrtani Pieri, Panayiota Demosthenous, Kyriakos Felekkis, Maria Arsali, Yiannis Athanasiou, Dimitris Xydakis, Kostas Stylianou, Eugenios Daphnis, Giorgos Goulielmos, Petros Loizou, Judith Savige, Martin Höhne, Linus A Völker, Thomas Benzing, Patrick H Maxwell, Daniel P Gale, Mathias Gorski, Carsten Böger, Barbara Kollerits, Florian Kronenberg, Bernhard Paulweber, Michalis Zavros, Alkis Pierides, Constantinos Deltas
BACKGROUND: Recent data emphasize that thin basement membrane nephropathy (TBMN) should not be viewed as a form of benign familial hematuria since chronic renal failure (CRF) and even end-stage renal disease (ESRD), is a possible development for a subset of patients on long-term follow-up, through the onset of focal and segmental glomerulosclerosis (FSGS). We hypothesize that genetic modifiers may explain this variability of symptoms. METHODS: We looked in silico for potentially deleterious functional SNPs, using very strict criteria, in all the genes significantly expressed in the slit diaphragm (SD)...
2017: PloS One
https://www.readbyqxmd.com/read/28331185/the-role-of-angiotensin-ii-in-glomerular-volume-dynamics-and-podocyte-calcium-handling
#9
Daria V Ilatovskaya, Oleg Palygin, Vladislav Levchenko, Bradley T Endres, Alexander Staruschenko
Podocytes are becoming a primary focus of research efforts due to their association with progressive glomeruli damage in disease states. Loss of podocytes can occur as a result of excessive intracellular calcium influx, and we have previously shown that angiotensin II (Ang II) via canonical transient receptor potential 6 (TRPC6) channels caused increased intracellular Ca(2+) flux in podocytes. We showed here with patch-clamp electrophysiology that Ang II activates TRPC channels; then using confocal calcium imaging we demonstrated that Ang II-dependent stimulation of Ca(2+) influx in the podocytes is precluded by blocking either AT1 or AT2 receptors (ATRs)...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28329012/tracking-the-stochastic-fate-of-cells-of-the-renin-lineage-after-podocyte-depletion-using-multicolor-reporters-and-intravital-imaging
#10
Natalya V Kaverina, Hiroyuki Kadoya, Diana G Eng, Michael E Rusiniak, Maria Luisa S Sequeira-Lopez, R Ariel Gomez, Jeffrey W Pippin, Kenneth W Gross, Janos Peti-Peterdi, Stuart J Shankland
Podocyte depletion plays a major role in focal segmental glomerular sclerosis (FSGS). Because cells of the renin lineage (CoRL) serve as adult podocyte and parietal epithelial cell (PEC) progenitor candidates, we generated Ren1cCre/R26R-ConfettiTG/WT and Ren1dCre/R26R-ConfettiTG/WT mice to determine CoRL clonality during podocyte replacement. Four CoRL reporters (GFP, YFP, RFP, CFP) were restricted to cells in the juxtaglomerular compartment (JGC) at baseline. Following abrupt podocyte depletion in experimental FSGS, all four CoRL reporters were detected in a subset of glomeruli at day 28, where they co-expressed de novo four podocyte proteins (podocin, nephrin, WT-1 and p57) and two glomerular parietal epithelial cell (PEC) proteins (claudin-1, PAX8)...
2017: PloS One
https://www.readbyqxmd.com/read/28325697/alcam-a-novel-biomarker-in-patients-with-type-2-diabetes-mellitus-complicated-with-diabetic-nephropathy
#11
Alba Sulaj, Stefan Kopf, Elisabeth Gröne, Hermann-Josef Gröne, Sigrid Hoffmann, Erwin Schleicher, Hans-Ulrich Häring, Vedat Schwenger, Stephan Herzig, Thomas Fleming, Peter P Nawroth, Rüdiger von Bauer
BACKGROUND & AIM: Activated leukocyte cell adhesion molecule (ALCAM/CD166) functions analogue to the receptor of advanced glycation end products, which has been implicated in the development of diabetic nephropathy (DN). We investigated the expression of ALCAM and its ligand S100B in patients with DN. METHODS: A total of 34 non-diabetic patients, 29 patients with type 2 diabetes and normal albuminuria and 107 patients with type 2 diabetes complicated with DN were assessed for serum concentration of soluble ALCAM (sALCAM) by ELISA...
January 21, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28320523/roles-of-fluid-shear-stress-and-retinoic-acid-in-the-differentiation-of-primary-cultured-human-podocytes
#12
Seung Hee Yang, Jin Woo Choi, Dongeun Huh, Hyung Ah Jo, Sejoong Kim, Chun Soo Lim, Jung Chan Lee, Hee Chan Kim, Hyug Moo Kwon, Chang Wook Jeong, Cheol Kwak, Kwon Wook Joo, Yon Su Kim, Dong Ki Kim
Due to the distinct features that distinguish immortalized podocyte cell lines from their in vivo counterparts, primary cultured human podocytes might be a superior cell model for glomerular disease studies. However, the podocyte de-differentiation that occurs in culture remains an unresolved problem. Here, we present a method to differentiate primary cultured podocytes using retinoic acid (RA) and fluid shear stress (FSS), which mimic the in vivo environment of the glomerulus. RA treatment induced changes in the cell shape of podocytes from a cobblestone-like morphology to an arborized configuration with enhanced mobility...
March 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28318634/dna-methyltransferase-1-may-be-a-therapy-target-for-attenuating-diabetic-nephropathy-and-podocyte-injury
#13
Li Zhang, Qianmei Zhang, Shuangxin Liu, Yuanhan Chen, Ruizhao Li, Ting Lin, Chunping Yu, Hong Zhang, Zhongshun Huang, Xinchen Zhao, Xiaofan Tan, Zhuo Li, Zhiming Ye, Jianchao Ma, Bin Zhang, Wenjian Wang, Wei Shi, Xinling Liang
The contribution of DNA methylation to diabetic nephropathy, especially the effect on podocyte integrity, is not clarified. Here we found that albuminuria in a db/db mouse model was markedly attenuated after treatment with a DNA methylation inhibitor. This was accompanied by alleviation of glomerular hypertrophy, mesangial matrix expansion, and podocyte injury. The expression of DNA methyltransferase 1 (Dnmt1), nuclear factor Sp1, and nuclear factor kappa B (NFκB)-p65 markedly increased in podocytes in vivo and in vitro under the diabetic state...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28318628/b-and-t-cell-subpopulations-in-patients-with-severe-idiopathic-membranous-nephropathy-may-predict-an-early-response-to-rituximab
#14
Michelle Rosenzwajg, Eva Languille, Hanna Debiec, Joana Hygino, Karine Dahan, Tabassome Simon, David Klatzmann, Pierre Ronco
Primary membranous nephropathy (PMN) is characterized by antibodies to the podocyte, but little is known about B- and T-cell populations and their response to rituximab is controversial. To help resolve this we compared 33 lymphocyte subpopulations and 27 cytokines/chemokines in 25 patients with severe PMN and 27 age-matched healthy individuals. At baseline, patients had a significantly increased percentage of naive B-cells with significantly decreased switched and non-switched memory B-cells. There was a significantly decreased percentage of natural killer (NK) cells with an increase in the CD56(bright)CD16(-/lo) NK subset...
March 15, 2017: Kidney International
https://www.readbyqxmd.com/read/28315934/gas1-expression-in-parietal-cells-of-bowman-s-capsule-in-experimental-diabetic-nephropathy
#15
Brenda I Luna-Antonio, Rafael Rodriguez-Muñoz, Carmen Namorado-Tonix, Paula Vergara, Jose Segovia, Jose L Reyes
Gas1 (Growth Arrest-Specific 1) is a pleiotropic protein with novel functions including anti-proliferative and proapoptotic activities. In the kidney, the expression of Gas1 has been described in mesangial cells. In this study, we described that renal parietal cells of Bowman's capsule (BC) and the distal nephron cells also express Gas1. The role of Gas1 in the kidney is not yet known. There is a subpopulation of progenitor cells in Bowman's capsule with self-renewal properties which can eventually differentiate into podocytes as a possible mechanism of regeneration in the early stages of diabetic nephropathy...
March 18, 2017: Histochemistry and Cell Biology
https://www.readbyqxmd.com/read/28315862/the-evolving-role-of-rituximab-in-adult-minimal-change-glomerulopathy
#16
Landon C Brown, Meghan A Jobson, Fernanda Payan Schober, Emily H Chang, Ronald J Falk, Patrick H Nachman, William F Pendergraft
BACKGROUND: Minimal-change glomerulopathy is defined histologically by the presence of normal glomeruli on light microscopy and diffuse podocyte effacement on electron microscopy. Although effective in children, corticosteroid treatment in adults is more variable and time to response can be prolonged. Data to support rituximab use in adults with corticosteroid-dependent or resistant minimal-change glomerulopathy are limited. Here, we describe the clinical course of adults with corticosteroid-dependent or -resistant minimal-change glomerulopathy who received rituximab...
March 18, 2017: American Journal of Nephrology
https://www.readbyqxmd.com/read/28315733/wt1-ameliorates-podocyte-injury-via-repression-of-ezh2-%C3%AE-catenin-pathway-in-diabetic-nephropathy
#17
Jiao Wan, Xiaoyan Hou, Zhanmei Zhou, Jian Geng, Jianwei Tian, Jing Nie, Xiaoyan Bai
Epigenetic modulation of podocyte injury plays a pivotal role in diabetic nephropathy (DN). Wilm's tumor 1 (WT1) has been found to have opposing roles with β-catenin in podocyte biology. Herein, we asked whether the histone methyltransferase enzyme enhancer of zeste homolog 2 (EZH2) promotes WT1-induced podocyte injury via β-catenin activation and the underlying mechanisms. We found that WT1 antagonized EZH2 and ameliorated β-catenin-mediated podocyte injury as demonstrated by attenuated podocyte mesenchymal transition, maintenance of podocyte architectural integrity, decreased podocyte apoptosis and oxidative stress...
March 15, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28314927/enhanced-podocyte-vesicle-transport-in-the-nephrotic-rat
#18
Akihiro Tojo, Saaya Hatakeyama, Satoshi Kinugasa, Satoru Fukuda, Toshio Sakai
Albumin endocytosis is enhanced in the podocytes of minimal change nephrotic syndrome. We investigated that the endocytic vesicle transport in the podocyte using three-dimensional observation in a rat model of puromycin aminonucleoside (PAN)-induced nephrotic syndrome. At day 7, Evans Blue-labeled albumin was intravenously injected in PAN rats, and one kidney was fixed for a morphological analysis; the other was used for the isolation of glomeruli through sieving and protein analyses. Evans Blue-labeled albumin was found to accumulate in an increased number of vesicles in the podocytes of PAN rat...
March 17, 2017: Medical Molecular Morphology
https://www.readbyqxmd.com/read/28306565/can-podocytes-be-regenerated-in-adults
#19
Stuart J Shankland, Benjamin S Freedman, Jeffrey W Pippin
PURPOSE OF REVIEW: Podocytes are critical components of the nephron filtration barrier and are depleted in many kidney injuries and disease states. Terminally differentiated adult podocytes are highly specialized, postmitotic cells, raising the question of whether the body has any ability to regenerate lost podocytes. This timely question has recently been illuminated by a series of innovative studies. Here, we review recent progress on this topic of significant interest and debate. RECENT FINDINGS: The innovation of genetic labeling techniques enables fate tracing of individual podocytes, providing the strongest evidence yet that podocytes can be replaced by nearby progenitor cells...
March 16, 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/28301477/fragility-of-foot-process-morphology-in-kidney-podocytes-arises-from-chaotic-spatial-propagation-of-cytoskeletal-instability
#20
Cibele V Falkenberg, Evren U Azeloglu, Mark Stothers, Thomas J Deerinck, Yibang Chen, John C He, Mark H Ellisman, James C Hone, Ravi Iyengar, Leslie M Loew
Kidney podocytes' function depends on finger-like projections (foot processes) that interdigitate with those from neighboring cells to form the glomerular filtration barrier. The integrity of the barrier depends on spatial control of dynamics of actin cytoskeleton in the foot processes. We determined how imbalances in regulation of actin cytoskeletal dynamics could result in pathological morphology. We obtained 3-D electron microscopy images of podocytes and used quantitative features to build dynamical models to investigate how regulation of actin dynamics within foot processes controls local morphology...
March 16, 2017: PLoS Computational Biology
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