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https://www.readbyqxmd.com/read/28100501/mdm2-mediates-fibroblast-activation-and-renal-tubulointerstitial-fibrosis-via-p53-independent-pathway
#1
Chen Ye, Hui Tang, Zheng Zhao, Chun-Tao Lei, Chao-Qun You, Jiao Zhang, Pan Gao, Fang-Fang He, Shan Chen, Yumei Wang, Chun Zhang, Hua Su
It is well-recognized that Murine Double Minute gene 2 (MDM2) plays a critical role in cell proliferation and inflammatory processes during tumorigenesis. Also it is reported that MDM2 is expressed in glomeruli and involved in podocyte injury. However, whether MDM2 is implicated in renal fibrosis remains unclear. Here we investigated the role of MDM2 in tubulointerstitial fibrosis (TIF). By immunohistochemical staining and western blotting we confirmed that MDM2 is up-regulated in tubulointerstitial compartment in TIF patients and Unilateral Urethral Obstruction (UUO) mice, which mainly originates from myofibroblasts...
January 18, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28078490/podocalyxin-as-a-major-pluripotent-marker-and-novel-keratan-sulfate-proteoglycan-in-human-embryonic-and-induced-pluripotent-stem-cells
#2
REVIEW
Hidenao Toyoda, Yuko Nagai, Aya Kojima, Akiko Kinoshita-Toyoda
Podocalyxin (PC) was first identified as a heavily sialylated transmembrane protein of glomerular podocytes. Recent studies suggest that PC is a remarkable glycoconjugate that acts as a universal glyco-carrier. The glycoforms of PC are responsible for multiple functions in normal tissue, human cancer cells, human embryonic stem cells (hESCs), and human induced pluripotent stem cells (hiPSCs). PC is employed as a major pluripotent marker of hESCs and hiPSCs. Among the general antibodies for human PC, TRA-1-60 and TRA-1-81 recognize the keratan sulfate (KS)-related structures...
January 11, 2017: Glycoconjugate Journal
https://www.readbyqxmd.com/read/28069388/vitamin-d-receptor-deficit-induces-activation-of-renin-angiotensin-system-via-sirt1-modulation-in-podocytes
#3
Nirupama Chandel, Kamesh Ayosolla, Hongxiu Wen, Xiqian Lan, Shabirul Haque, Moin A Saleem, Ashwani Malhotra, Pravin C Singhal
Vitamin D receptor (VDR) deficient status has been shown to be associated with the activation of renin angiotensin system (RAS). We hypothesized that lack of VDR would enhance p53 expression in podocytes through down regulation of SIRT1; the former would enhance the transcription of angiotensinogen (Agt) and angiotensinogen II type 1 receptor (AT1R) leading to the activation of RAS. Renal tissues of VDR mutant (M) mice displayed increased expression of p53, Agt, renin, and AT1R. In vitro studies, VDR knockout podocytes not only displayed up regulation p53 but also displayed enhanced expression of Agt, renin and AT1R...
January 6, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28065518/membranous-nephropathy-integrating-basic-science-into-improved-clinical-management
#4
REVIEW
Daniel C Cattran, Paul E Brenchley
Idiopathic membranous nephropathy (INM) remains a common cause of the nephrotic syndrome in adults. The autoimmune nature of IMN was clearly delineated in 2009 with the identification of the glomerular-deposited IgG to be a podocyte receptor, phospholipase A2 receptor (PLA2R) in 70% to 75% of cases. This anti-PLA2R autoantibody, predominantly the IgG4 subclass, has been quantitated in serum using an enzyme-linked immunosorbent assay and has been used to aid diagnosis and monitor response to immunosuppressive therapy...
January 5, 2017: Kidney International
https://www.readbyqxmd.com/read/28063735/nephrotic-syndrome-in-small-cell-lung-cancer-and-induction-of-c-mip-in-podocytes
#5
Yassine Bouatou, Thibaud Koessler, Julie Oniszczuk, Shao-Yu Zhang, Solange Moll, Vincent Audard, Sophie de Seigneux, Djillali Sahali
Paraneoplastic nephrotic syndrome is often a complication in patients with cancer, and various histologic lesions have been described in the kidney. We report the case of a 76-year-old woman who presented with a podocytopathy that was found to be associated with a small cell lung carcinoma (SCLC). One cycle of carboplatin-etoposide combination therapy led to resolution of nephrotic syndrome and remission of the lung carcinoma. C-Maf-inducing protein (C-Mip) was overexpressed in both podocytes and cancer cells, but was not found in control kidney and lung tissue samples...
January 4, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28063595/the-mitochondrial-targeted-peptide-ss-31-improves-glomerular-architecture-in-mice-of-advanced-age
#6
Mariya T Sweetwyne, Jeffrey W Pippin, Diana G Eng, Kelly L Hudkins, Ying Ann Chiao, Matthew D Campbell, David J Marcinek, Charles E Alpers, Hazel H Szeto, Peter S Rabinovitch, Stuart J Shankland
Although age-associated changes in kidney glomerular architecture have been described in mice and man, the mechanisms are unknown. It is unclear if these changes can be prevented or even reversed by systemic therapies administered at advanced age. Using light microscopy and transmission electron microscopy, our results showed glomerulosclerosis with injury to mitochondria in glomerular epithelial cells in mice aged 26 months (equivalent to a 79-year-old human). To test the hypothesis that reducing mitochondrial damage in late age would result in lowered glomerulosclerosis, we administered the mitochondrial targeted peptide, SS-31, to aged mice...
January 4, 2017: Kidney International
https://www.readbyqxmd.com/read/28059119/dysregulation-of-wti-kts-is-associated-with-the-kidney-specific-effects-of-the-lmx1b-r246q-mutation
#7
Gentzon Hall, Brandon Lane, Megan Chryst-Ladd, Guanghong Wu, Jen-Jar Lin, XueJun Qin, Elizabeth R Hauser, Rasheed Gbadegesin
Mutations in the LIM homeobox transcription factor 1-beta (LMX1B) are a cause of nail patellar syndrome, a condition characterized by skeletal changes, glaucoma and focal segmental glomerulosclerosis. Recently, a missense mutation (R246Q) in LMX1B was reported as a cause of glomerular pathologies without extra-renal manifestations, otherwise known as nail patella-like renal disease (NPLRD). We have identified two additional NPLRD families with the R246Q mutation, though the mechanisms by which LMX1BR246Q causes a renal-specific phenotype is unknown...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28053698/vincristine-alleviates-adriamycin-induced-nephropathy-through-stabilizing-actin-cytoskeleton
#8
Lei Yin, Youying Mao, Hejie Song, Ye Wang, Wei Zhou, Zhen Zhang
Antimicrotubule agent vincristine (VCR) has long been known as an alternative treatment for frequent relapse nephrotic syndrome and steroid-dependent nephrotic syndrome (SDNS). However, the mechanism is unknown. Here we found that VCR at a dosage much lower than that as an antimicrotubule agent can alleviate adriamycin (ADR)-induced proteinuria and podocyte foot process effacement. In cultured podocytes, VCR prevents ADR-induced actin fiber disorganization. In both in vitro and in vivo models, VCR suppresses ADR-induced overexpression of α3β1 integrin and focal adhesion kinase (FAK)...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28052869/nlrp3-inflammasome-activation-contributes-to-aldosterone-induced-podocyte-injury
#9
Mi Bai, Ying Chen, Min Zhao, Yue Zhang, John Cijiang He, Songming Huang, Zhanjun Jia, Aihua Zhang
Aldosterone (Aldo) has been shown as an important contributor of podocyte injury. However, the underlying molecular mechanisms are still elusive. Recently, the pathogenic role of NLRP3 inflammasome in mediating renal tubular damage was identified while its role in podocyte injury still needs evidence. Thus the present study was undertaken to investigate the role of NLRP3 inflammasome in Aldo-induced podocyte damage. In vitro, exposure of podocytes to Aldo enhanced NLRP3, caspase-1 and IL-18 expressions in dose- and time-dependent manners, indicating an activation of NLRP3 inflammasome, which was significantly blocked by a mineralocorticoid receptor antagonist Eplerenone (EPL) or an antioxidant NAC...
January 4, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28051762/impact-of-long-term-high-fat-diet-intake-gestational-protein-restricted-offspring-on-kidney-morphology-and-function
#10
V H G Rizzi, L D B Sene, C D B Fernandez, J A R Gontijo, P A Boer
Emerging evidence highlights the far-reaching consequences of high-fat diet (HFD) and obesity on kidney morphological and functional disorders. In the present study, we aim to evaluate the effects of early HFD intake on renal function and morphology in maternal protein-restricted offspring (LP). LP and normal protein-intake offspring (NP) were fed HFD (LPH and NPH, respectively) or standard rodent (LPN and NPN) diet from the 8th to 13th week of age. Blood pressure, kidney function, immunohistochemistry and scanning electron microscopy were analyzed...
February 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28028935/renoprotection-focus-on-trpv1-trpv4-trpc6-and-trpm2
#11
REVIEW
L Markó, M Mannaa, T N Haschler, S Krämer, M Gollasch
Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca(2+) influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS)...
November 7, 2016: Acta Physiologica
https://www.readbyqxmd.com/read/28028615/podocyte-number-and-density-changes-during-early-human-life
#12
Masao Kikuchi, Larysa Wickman, Raja Rabah, Roger C Wiggins
BACKGROUND: Podocyte depletion, which drives progressive glomerulosclerosis in glomerular diseases, is caused by a reduction in podocyte number, size or function in the context of increasing glomerular volume. METHODS: Kidneys obtained at autopsy from premature and mature infants who died in the first year of life (n = 24) were used to measure podometric parameters for comparison with previously reported data from older kidneys. RESULTS: Glomerular volume increased 4...
December 27, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28025032/the-metabolic-syndrome-and-chronic-kidney-disease
#13
REVIEW
Xin Zhang, Lilach O Lerman
The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including insulin resistance (IR), dyslipidemia, and hypertension, which may also foster development of chronic kidney disease. The mechanisms of MetS-induced kidney disease are not fully understood. The purpose of this review is to summarize recent discoveries regarding the impact of MetS on the kidney, particularly on the renal microvasculature and cellular mitochondria. Fundamental manifestations of MetS include IR and adipose tissue expansion, the latter promoting chronic inflammation and oxidative stress that exacerbate IR...
December 9, 2016: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28024901/cyclin-dependent-kinase-5-contributes-to-endoplasmic-reticulum-stress-induced-podocyte-apoptosis-via-promoting-mekk1-phosphorylation-at-ser280-in-diabetic-nephropathy
#14
Yue Zhang, Xiang Gao, Shuanggang Chen, Min Zhao, Jing Chen, Rui Liu, Shengyang Cheng, Mengyuan Qi, Shuo Wang, Wei Liu
Endoplasmic reticulum (ER) stress has been reported to be associated with podocyte apoptosis in diabetic nephropathy, but the mechanism of ER signaling in podocyte apoptosis hasn't been fully understood. Our previous studies have demonstrated that Cyclin-dependent kinase 5 (Cdk5) was associated with podocyte apoptosis in diabetic nephropathy. The present study was designed to examine whether and how Cdk5 activity plays a role in ER stress induced podocyte apoptosis in diabetic nephropathy. The results showed that along with induction of Cdk5 and apoptosis, GRP78 and its two sensors as well as CHOP and cleaved caspase-12 were induced in high glucose treated podocytes...
December 24, 2016: Cellular Signalling
https://www.readbyqxmd.com/read/28017719/repression-of-mir-217-protects-against-high-glucose-induced-podocyte-injury-and-insulin-resistance-by-restoring-pten-mediated-autophagy-pathway
#15
Juan Sun, Zhao Pin Li, Rui Qin Zhang, Hui Min Zhang
Podocyte damage is the initial hallmark of diabetic nephropathy (DN), leading to the increasing morbidity and mortality in diabetic patients. Recent researches have corroborated the critical roles of miRNAs in the pathological progression of DN. Here, elevation of miR-217 was verified in high glucose (HG)-stimulated podocytes. Moreover, blocking miR-217 expression antagonized HG-induced cell injury by attenuating the adverse role of HG on cell viability and inhibiting ROS levels and cell apoptosis. Simultaneously, miR-217 repression restored HG-disrupted insulin resistance by elevating glucose uptake and nephrin expression, an essential component for insulin-induced glucose uptake...
December 23, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28011197/septin-7-reduces-nonmuscle-myosin-iia-activity-in-the-snap23-complex-and-hinders-glut4-storage-vesicle-docking-and-fusion
#16
Anita A Wasik, Vincent Dumont, Jukka Tienari, Tuula A Nyman, Christopher L Fogarty, Carol Forsblom, Markku Lehto, Eero Lehtonen, Per-Henrik Groop, Sanna Lehtonen
Glomerular epithelial cells, podocytes, are insulin responsive and can develop insulin resistance. Here, we demonstrate that the small GTPase septin 7 forms a complex with nonmuscle myosin heavy chain IIA (NMHC-IIA; encoded by MYH9), a component of the nonmuscle myosin IIA (NM-IIA) hexameric complex. We observed that knockdown of NMHC-IIA decreases insulin-stimulated glucose uptake into podocytes. Both septin 7 and NM-IIA associate with SNAP23, a SNARE protein involved in GLUT4 storage vesicle (GSV) docking and fusion with the plasma membrane...
December 20, 2016: Experimental Cell Research
https://www.readbyqxmd.com/read/28005239/combination-of-cilostazol-and-probucol-protected-podocytes-from-lipopolysaccharide-induced-injury-by-both-anti-inflammatory-and-anti-oxidative-mechanisms
#17
Peng He, Harukiyo Kawamura, Minoru Takemoto, Yoshiro Maezawa, Takahiro Ishikawa, Ryoichi Ishibashi, Kenichi Sakamoto, Mayumi Shoji, Akiko Hattori, Masaya Yamaga, Shintaro Ide, Kana Ide, Aiko Hayashi, Hirotake Tokuyama, Kazuki Kobayashi, Koutaro Yokote
Podocytes are essential for maintaining kidney glomerular functions. Injuries to podocyte are closely related to the pathological process of proteinuria. However, a treatment for podocyte injury has still not been established. Cilostazol (CSZ) and probucol (PBC) have been shown to possess renoprotective effects. Therefore, we evaluated these drugs in a lipopolysaccharide (LPS)-induced podocyte injury model. 7-week-old female C57BL/6J mice were fed a normal diet or a diet containing 0.3% CSZ, 0.5% PBC, or both for 10 days...
December 22, 2016: Journal of Nephrology
https://www.readbyqxmd.com/read/28004272/rice-bran-protein-hydrolysates-attenuate-diabetic-nephropathy-in-diabetic-animal-model
#18
Kampeebhorn Boonloh, Eun Soo Lee, Hong Min Kim, Mi Hye Kwon, You Mi Kim, Patchareewan Pannangpetch, Bunkerd Kongyingyoes, Upa Kukongviriyapan, Supawan Thawornchinsombut, Eun Young Lee, Veerapol Kukongviriyapan, Choon Hee Chung
INTRODUCTION: Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. METHODS: Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks...
December 21, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/28004150/assessment-of-urinary-microparticles-in-normotensive-patients-with-type-1-diabetes
#19
Yuliya Lytvyn, Fengxia Xiao, Christopher R J Kennedy, Bruce A Perkins, Heather N Reich, James W Scholey, David Z Cherney, Dylan Burger
AIMS/HYPOTHESIS: Assessment of urinary extracellular vesicles including exosomes and microparticles (MPs) is an emerging approach for non-invasive detection of renal injury. We have previously reported that podocyte-derived MPs are increased in diabetic mice in advance of albuminuria. Here, we hypothesised that type 1 diabetes and acute hyperglycaemia would increase urinary podocyte MP levels in uncomplicated diabetes. METHODS: In this post hoc exploratory analysis, we examined archived urine samples from normoalbuminuric patients with uncomplicated type 1 diabetes studied under clamped euglycaemia and hyperglycaemia and compared with healthy controls...
December 21, 2016: Diabetologia
https://www.readbyqxmd.com/read/27998979/alpha-actinin-4-actn4-regulates-glucocorticoid-receptor-mediated-transactivation-and-transrepression-in-podocytes
#20
Xuan Zhao, Simran Khurana, Sharmistha Charkraborty, Yuqian Tian, John R Sedor, Leslie A Bruggeman, Hung-Ying Kao
Glucocorticoids (GCs) are a general class of steroids that possess renoprotective activity in glomeruli through their interaction with the glucocorticoid receptor. However, the mechanisms by which the GCs ameliorate proteinuria and glomerular disease are not well understood. In this study, we demonstrated that alpha actinin 4 (ACTN4), an actin-crosslinking protein known to coordinate cytoskeletal organization, interacts with the glucocorticoid receptor (GR) in the nucleus of human podocytes (HPCs), a key cell type in the glomerulus critical for kidney filtration function...
December 20, 2016: Journal of Biological Chemistry
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