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Podocyte disease

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https://www.readbyqxmd.com/read/29674631/orally-active-species-independent-novel-a-3-adenosine-receptor-antagonist-protects-against-kidney-injury-in-db-db-mice
#1
Debra Dorotea, Ahreum Cho, Gayoung Lee, Guideock Kwon, Junghwa Lee, Pramod K Sahu, Lak Shin Jeong, Dae Ryong Cha, Hunjoo Ha
Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and the current pharmacological treatment for DKD is limited to renin-angiotensin system (RAS) inhibitors. Adenosine is detectable in the kidney and is significantly elevated in response to cellular damage. While all 4 known subtypes of adenosine receptors, namely, A1 AR, A2a AR, A2b AR, and A3 AR, are expressed in the kidney, our previous study has demonstrated that a novel, orally active, species-independent, and selective A3 AR antagonist, LJ-1888, ameliorates unilateral ureteral obstruction-induced tubulointerstitial fibrosis...
April 20, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29673759/alport-syndrome-and-pierson-syndrome-diseases-of-the-glomerular-basement-membrane
#2
REVIEW
Steven D Funk, Meei-Hua Lin, Jeffrey H Miner
The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy...
April 16, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29629372/glomerular-endothelial-cells-stress-and-cross-talk-with-podocytes-in-the-development-of-diabetic-kidney-disease
#3
REVIEW
Ilse Sofia Daehn
Diabetic kidney disease (DKD) is one of the major causes of morbidity and mortality in diabetic patients and also the leading single cause of end-stage renal disease in the United States. A large proportion of diabetic patients develop DKD and others don't, even with comparable blood glucose levels, indicating a significant genetic component of disease susceptibility. The glomerulus is the primary site of diabetic injury in the kidney, glomerular hypertrophy and podocyte depletion are glomerular hallmarks of progressive DKD, and the degree of podocyte loss correlates with severity of the disease...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29629277/weight-loss-has-an-additive-effect-on-the-proteinuria-reduction-of-angiotensin-ii-receptor-blockers-in-hypertensive-patients-with-chronic-kidney-disease
#4
Shin Young Ahn, Dong Ki Kim, Seung Seok Han, Jung Hwan Park, Sung Joon Shin, Sang Ho Lee, Bum Soon Choi, Chun Soo Lim, Suhnggwon Kim, Ho Jun Chin
Background: Weight reduction is a lifestyle intervention that has been introduced for prevention and management of chronic kidney disease (CKD). We investigate the additive anti-proteinuric effect of weight reduction on the usage of angiotensin II receptor blockers (ARBs) and its potential mechanisms in hypertensive CKD patients. Methods: This study is a subanalysis of data from an open-label, randomized, controlled clinical trial. Among the 235 participants, 227 were assigned to subgroups according to changes in body weight...
March 2018: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/29608912/glomerular-mitochondrial-changes-in-hiv-associated-renal-injury
#5
Joseph L Bryant, Poornachander R Guda, Girma Asemu, Rogin Subedi, Sugata Ray, Omar S Khalid, Vivek Shukla, Dhruvil Patel, Harry Davis, Vamshi K C Nimmagadda, Tapas K Makar
HIV-associated nephropathy (HIVAN) is an AIDs-related disease of the kidney. HIVAN is characterized by severe proteinuria, podocyte hyperplasia, collapse, glomerular, and tubulointerstitial damage. HIV-1 transgenic (Tg26) mouse is the most popular model to study the HIV manifestations that develop similar renal presentations as HIVAN. Viral proteins, including Tat, Nef, and Vpr play a significant role in renal cell damage. It has been shown that mitochondrial changes are involved in several kidney diseases, and therefore, mitochondrial dysfunction may be implicated in the pathology of HIVAN...
March 30, 2018: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/29602395/the-role-of-peroxisome-proliferator-activated-receptor-%C3%AE-coactivator-1%C3%AE-pgc-1%C3%AE-in-kidney-disease
#6
REVIEW
Szu-Yuan Li, Katalin Susztak
Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is a key transcriptional regulator of mitochondrial biogenesis and function. Several recent studies have evaluated the role of PGC-1α in various renal cell types in healthy and disease conditions. Renal tubule cells mostly depend on mitochondrial fatty acid oxidation for energy generation. A decrease in PGC-1α expression and fatty acid oxidation is commonly observed in patient samples and mouse models with acute and chronic kidney disease...
March 2018: Seminars in Nephrology
https://www.readbyqxmd.com/read/29600408/independent-regulation-of-renin-angiotensin-aldosterone-system-in-the-kidney
#7
REVIEW
Akira Nishiyama, Hiroyuki Kobori
Renin-angiotensin-aldosterone system (RAAS) plays important roles in regulating renal hemodynamics and functions, as well as in the pathophysiology of hypertension and renal disease. In the kidney, angiotensin II (Ang II) production is controlled by independent multiple mechanisms. Ang II is compartmentalized in the renal interstitial fluid with much higher concentrations than those existing in the circulation. Inappropriate activation of the intrarenal RAAS is an important contributor to the pathogenesis of hypertension and renal injury...
March 29, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29594119/monogenic-causes-of-proteinuria-in-children
#8
REVIEW
Onur Cil, Farzana Perwad
Glomerular disease is a common cause for proteinuria and chronic kidney disease leading to end-stage renal disease requiring dialysis or kidney transplantation in children. Nephrotic syndrome in children is diagnosed by the presence of a triad of proteinuria, hypoalbuminemia, and edema. Minimal change disease is the most common histopathological finding in children and adolescents with nephrotic syndrome. Focal segmental sclerosis is also found in children and is the most common pathological finding in patients with monogenic causes of nephrotic syndrome...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29575816/kidney-derived-c-kit-cells-possess-regenerative-potential
#9
Samirah A Gomes, Joshua M Hare, Erika B Rangel
Kidney-derived c-Kit+ cells exhibit progenitor/stem cell properties in vitro (self-renewal capacity, clonogenicity, and multipotentiality). These cells can regenerate epithelial tubular cells following ischemia-reperfusion injury and accelerate foot processes effacement reversal in a model of acute proteinuria in rats. Several mechanisms are involved in kidney regeneration by kidney-derived c-Kit+ cells, including cell engraftment and differentiation into renal-like structures, such as tubules, vessels, and podocytes...
April 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29574897/il-6-increases-podocyte-motility-via-mlc-mediated-focal-adhesion-impairment-and-cytoskeleton-disassembly
#10
Fang-Fang He, Dian Bao, Hua Su, Yu-Mei Wang, Chun-Tao Lei, Chun-Yun Zhang, Chen Ye, Hui Tang, Cheng Wan, Chao-Qun You, Jiao Zhang, Jing Xiong, Chun Zhang
The disturbance of podocyte motility is an essential pathogenic mechanisms of foot process effacement during proteinuric diseases, and myosin light chain (MLC) is a pivotal component in regulating the motility of podocytes. Inflammatory cytokine interleukin-6 (IL-6) has been reported to induce podocyte abnormalities by various mechanisms, however, whether aberrant cell motility contributes to the IL-6-induced podocyte injury remains unknown. Here, by wound healing, transwell, and cell migration assays, we confirmed that IL-6 accelerates the motility of podocyte...
March 25, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29574544/preservation-of-renal-function-in-chronic-diabetes-by-enhancing-glomerular-glucose-metabolism
#11
REVIEW
Weier Qi, Qian Li, Daniel Gordin, George L King
Diabetic nephropathy (DN) affects approximately 30-40% of patients with type 1 (T1DM) and type 2 diabetes (T2DM). It is a major cause of end-stage renal disease (ESRD) for the developed world. Hyperglycemia and genetics are major causal factors for the initiation and progression of DN. Multiple abnormalities in glucose and mitochondrial metabolism induced by diabetes likely contribute to the severity of DN. Recent clinical studies in people with extreme duration of T1DM (> 50 years, Joslin Medalist Study) have supported the importance of endogenous protective factors to neutralize the toxic effects of hyperglycemia on renal and other vascular tissues...
March 24, 2018: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/29572404/similar-biophysical-abnormalities-in-glomeruli-and-podocytes-from-two-distinct-models
#12
Addie E Embry, Zhenan Liu, Joel M Henderson, F Jefferson Byfield, Liping Liu, Joonho Yoon, Zhenzhen Wu, Katrina Cruz, Sara Moradi, C Barton Gillombardo, Rihanna Z Hussain, Richard Doelger, Olaf Stuve, Audrey N Chang, Paul A Janmey, Leslie A Bruggeman, R Tyler Miller
Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear. Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury...
March 23, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29559657/early-and-late-scanning-electron-microscopy-findings-in-diabetic-kidney-disease
#13
Sara Conti, Norberto Perico, Rubina Novelli, Camillo Carrara, Ariela Benigni, Giuseppe Remuzzi
Diabetic nephropathy (DN), the single strongest predictor of mortality in patients with type 2 diabetes, is characterized by initial glomerular hyperfiltration with subsequent progressive renal function loss with or without albuminuria, greatly accelerated with the onset of overt proteinuria. Experimental and clinical studies have convincingly shown that early interventions retard disease progression, while treatment if started late in the disease course seldom modifies the slope of GFR decline. Here we assessed whether the negligible renoprotection afforded by drugs in patients with proteinuric DN could be due to loss of glomerular structural integrity, explored by scanning electron microscopy (SEM)...
March 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29558749/fabry-nephropathy-an-evidence-based-narrative-review
#14
María Del Pino, Amado Andrés, Ana Ávila Bernabéu, Joaquín de Juan-Rivera, Elvira Fernández, Juan de Dios García Díaz, Domingo Hernández, José Luño, Isabel Martínez Fernández, José Paniagua, Manuel Posada de la Paz, José Carlos Rodríguez-Pérez, Rafael Santamaría, Roser Torra, Joan Torras Ambros, Pedro Vidau, Josep-Vicent Torregrosa
Fabry disease (FD) is a rare, X-linked disorder caused by mutations in the GLA gene encoding the enzyme α-galactosidase A. Complete or partial deficiency in this enzyme leads to intracellular accumulation of globotriaosylceramide (Gb3) and other glycosphingolipids in many cell types throughout the body, including the kidney. Progressive accumulation of Gb3 in podocytes, endothelial cells, epithelial cells, and tubular cells contribute to the renal symptoms of FD, which manifest as proteinuria and reduced glomerular filtration rate leading to renal insufficiency...
March 16, 2018: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29556761/recent-advances-of-animal-model-of-focal-segmental-glomerulosclerosis
#15
REVIEW
Jae Won Yang, Anne Katrin Dettmar, Andreas Kronbichler, Heon Yung Gee, Moin Saleem, Seong Heon Kim, Jae Il Shin
In the last decade, great advances have been made in understanding the genetic basis for focal segmental glomerulosclerosis (FSGS). Animal models using specific gene disruption of the slit diaphragm and cytoskeleton of the foot process mirror the etiology of the human disease. Many animal models have been developed to understand the complex pathophysiology of FSGS. Therefore, we need to know the usefulness and exact methodology of creating animal models. Here, we review classic animal models and newly developed genetic animal models...
March 20, 2018: Clinical and Experimental Nephrology
https://www.readbyqxmd.com/read/29549365/fyve-domain-containing-protein-zfyve28-regulates-egfr-signaling-in-podocytes-but-is-not-critical-for-the-function-of-filtration-barrier-in-mice
#16
Sonia Zambrano, Patricia Q Rodriguez, Jing Guo, Katja Möller-Hackbarth, Angelina Schwarz, Jaakko Patrakka
The kidney ultrafiltration barrier is formed of endothelial cells, the glomerular basement membrane and podocytes. Podocytes have a central role in normal physiology and disease pathogenesis of the glomerulus. Signaling through epidermal growth factor receptor (EGFR) in podocytes mediates development of many glomerular disease processes. In this work, we have identified zinc finger FYVE-type containing 28 (ZFYVE28) as a novel highly podocyte-enriched gene. We localize ZFYVE28 in podocyte foot processes in adult kidney...
March 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29547847/lipid-peroxidation-regulates-podocyte-migration-and-cytoskeletal-structure-through-redox-sensitive-rhoa-signaling
#17
Claudia Kruger, Susan J Burke, J Jason Collier, Trang-Tiffany Nguyen, J Michael Salbaum, Krisztian Stadler
Early podocyte loss is characteristic of chronic kidney diseases (CKD) in obesity and diabetes. Since treatments for hyperglycemia and hypertension do not prevent podocyte loss, there must be additional factors causing podocyte depletion. The role of oxidative stress has been implicated in CKD but it is not known how exactly free radicals affect podocyte physiology. To assess this relationship, we investigated the effects of lipid radicals on podocytes, as lipid peroxidation is a major form of oxidative stress in diabetes...
March 6, 2018: Redox Biology
https://www.readbyqxmd.com/read/29530281/single-nephron-proteomes-connect-morphology-and-function-in-proteinuric-kidney-disease
#18
Martin Höhne, Christian K Frese, Florian Grahammer, Claudia Dafinger, Giuliano Ciarimboli, Linus Butt, Julia Binz, Matthias J Hackl, Mahdieh Rahmatollahi, Martin Kann, Simon Schneider, Mehmet M Altintas, Bernhard Schermer, Thomas Reinheckel, Heike Göbel, Jochen Reiser, Tobias B Huber, Rafael Kramann, Tamina Seeger-Nukpezah, Max C Liebau, Bodo B Beck, Thomas Benzing, Andreas Beyer, Markus M Rinschen
In diseases of many parenchymatous organs, heterogeneous deterioration of individual functional units determines the clinical prognosis. However, the molecular characterization at the level of such individual subunits remains a technological challenge that needs to be addressed in order to better understand pathological mechanisms. Proteinuric glomerular kidney diseases are frequent and assorted diseases affecting a fraction of glomeruli and their draining tubules to variable extents, and for which no specific treatment exists...
March 9, 2018: Kidney International
https://www.readbyqxmd.com/read/29520569/mathematical-model-for-glucose-dependence-of-the-local-renin-angiotensin-system-in-podocytes
#19
Minu R Pilvankar, Michele A Higgins, Ashlee N Ford Versypt
Diabetic kidney disease (DKD) is the primary cause of kidney failure. Diabetic hyperglycemia primarily damages podocyte cells. Podocytes express a local renin-angiotensin system (RAS) that produces angiotensin II (ANG II). ANG II levels are elevated by hyperglycemia, triggering podocyte injury. Quantitative descriptions of glucose dose dependency of ANG II are scarce in the literature. For better understanding of the mechanism of glycemic injury in DKD, a mathematical model is developed to describe the glucose-stimulated local RAS in podocytes...
March 8, 2018: Bulletin of Mathematical Biology
https://www.readbyqxmd.com/read/29518610/zhen-wu-tang-protects-against-podocyte-injury-in-rats-with-iga-nephropathy-via-ppar%C3%AE-nf-%C3%AE%C2%BAb-pathway
#20
Bihao Liu, Yu He, Ruirui Lu, Jie Zhou, Lixia Bai, Peichun Zhang, Shufang Ye, Junbiao Wu, Chungling Liang, Yuan Zhou, Jiuyao Zhou
Zhen-wu-tang (ZWT) has been widely applied in chronic kidney diseases. However, the mechanism of ZWT remains unclear. Peroxisome proliferator-activated receptors-γ (PPARγ) is known as a protective factor for podocyte and kidney function. This study is aimed to investigate the protective effects of ZWT on IgA nephropathy (IgAN) in rats against podocyte injury and the underlying mechanism related to PPARγ. IgAN model rats were induced by administering bovine serum albumin, lipopolysaccharide, and carbon tetrachloride...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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