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https://www.readbyqxmd.com/read/29679791/phosphorodiamidate-morpholino-targeting-the-5-untranslated-region-of-the-zikv-rna-inhibits-virus-replication
#1
Waldemar Popik, Atanu Khatua, James E K Hildreth, Benjamin Lee, Donald J Alcendor
BACKGROUND: Zika virus (ZIKV) infection has been associated with microcephaly in infants. Currently there is no treatment or vaccine. Here we explore the use of a morpholino oligonucleotide targeted to the 5' untranslated region (5'-UTR) of the ZIKV RNA to prevent ZIKV replication. METHODS: Morpholino DWK-1 inhibition of ZIKV replication in human glomerular podocytes was examined by qRT-PCR, reduction in ZIKV genome copy number, western blot analysis, immunofluorescence and proinflammatory cytokine gene expression...
April 18, 2018: Virology
https://www.readbyqxmd.com/read/29678354/actin-dynamics-at-focal-adhesions-a-common-endpoint-and-putative-therapeutic-target-for-proteinuric-kidney-diseases
#2
REVIEW
Sanja Sever, Mario Schiffer
Proteinuria encompasses diverse causes including both genetic diseases and acquired forms such as diabetic and hypertensive nephropathy. The basis of proteinuria is a disturbance in size selectivity of the glomerular filtration barrier, which largely depends on the podocyte: a terminally differentiated epithelial cell type covering the outer surface of the glomerulus. Compromised podocyte structure is one of the earliest signs of glomerular injury. The phenotype of diverse animal models and podocyte cell culture firmly established the essential role of the actin cytoskeleton in maintaining functional podocyte structure...
April 17, 2018: Kidney International
https://www.readbyqxmd.com/read/29677049/urinary-podocyte-associated-molecules-and-albuminuria-in-hypertension
#3
Javier Perez-Hernandez, Maria D Olivares, Elena Solaz, Fernando Martinez, Sergio Martínez-Hervas, Gernot Pichler, Felipe J Chaves, Josep Redon, Raquel Cortes
OBJECTIVE: Hypertension-induced podocyte damage and the relationship with UAE is analyzed in diabetic and nondiabetic participants. PATIENTS AND METHODS: Sixty-four hypertensive patients, 30 diabetics, with glomerular filtration rate (eGFR) greater than 60 ml/min per 1.73 m were included. Urinary albumin excretion was measured in morning urine using a nephelometric immunoassay and expressed as albumin/creatinine ratio. Urinary pellets were obtained from fresh urine and mRNA was assessed by real-time quantitative PCR...
April 19, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29674631/orally-active-species-independent-novel-a-3-adenosine-receptor-antagonist-protects-against-kidney-injury-in-db-db-mice
#4
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
#5
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/29669318/neurod-expression-in-podocytes-and-interrelationships-with-nephrin-at-both-nuclear-and-cytoplasmic-sites
#6
Silvia Armelloni, Masami Ikehata, Deborah Mattinzoli, Min Li, Carlo Maria Alfieri, Mariapia Rastaldi, Piergiorgio Messa
Background/Aims The research of genes implicated in kidney glomerular function, eliciting cell fate program, is always at the forefront in nephrological studies. Several neurological molecules have been recently the object of study not only for their involvement in the central nervous system differentiation but also for their importance in the functionality of other organs and for mature phenotype, as in kidney. NeuroD, in CNS, is related to two functional roles, the early survival and the differentiation. The aim of our study was to ascertain the presence of NeuroD transcription factor in glomeruli and to understand which targets and mechanisms NeuroD controls...
April 13, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29660398/molecular-phenotypes-of-the-human-kidney-myoid-stromal-cells-telocytes-and-myoepithelial-cells
#7
M C Rusu, L Mogoantă, F Pop, M A Dobra
The connective stromal and epithelial compartments of the kidney have regenerative potential and phenotypic flexibility. A few studies have shown that cells appertaining to both compartments can exhibit myoid phenotypes. The purpose of our study was to investigate the myoid pattern of kidney and its association with the kidney niches containing stromal cells/telocytes (SC/TCs). We performed an immunohistochemical study using a panel of endothelial, myoid, mesenchymal and stem/progenitor markers, namely CD31, CD34, CD105 (endoglin), CD117/c-kit, nestin, desmin, α-smooth muscle actin (α-SMA) and the heavy chain of smooth muscle myosin (SMM)...
April 13, 2018: Annals of Anatomy, Anatomischer Anzeiger: Official Organ of the Anatomische Gesellschaft
https://www.readbyqxmd.com/read/29644057/clinical-and-pathological-phenotype-of-genetic-causes-of-focal-segmental-glomerulosclerosis-in-adults
#8
Nicola Lepori, Ladan Zand, Sanjeev Sethi, Gema Fernandez-Juarez, Fernando C Fervenza
Focal segmental glomerulosclerosis (FSGS) is a histologic lesion resulting from a variety of pathogenic processes that cause injury to the podocytes. Recently, mutations in more than 50 genes expressed in podocyte or glomerular basement membrane were identified as causing genetic forms of FSGS, the majority of which are characterized by onset in childhood. The prevalence of adult-onset genetic FSGS is likely to be underestimated and its clinical and histological features have not been clearly described. A small number of studies of adult-onset genetic FSGS showed that there is heterogeneity in clinical and histological findings, with a presentation ranging from sub-nephrotic proteinuria to full nephrotic syndrome...
April 2018: Clinical Kidney Journal
https://www.readbyqxmd.com/read/29643035/-correlation-between-expressions-of-vegf-and-trpc6-and-their-roles-in-podocyte-injury-in-rats-with-diabetic-nephropathy
#9
Xiao-Na Zhu, Yu-Huan Wang, Juan-Juan Wu, Peng Dong, Min Zhang
OBJECTIVE: To analyze the correlation between the expressions of vascular endothelial growth factor (VEGF) and transient receptor potential canonical 6 (TRPC6) and their role in podocyte injury in rats with diabetic nephropathy. METHODS: Forty SD rats with diabetic nephropathy induced by intraperitoneal injection of 65 mg/kg streptozotocin were randomized equally into 5 groups, including a diabetic nephropathy model group and 4 treatment groups, with 8 normal SD rats as the normal control group...
March 20, 2018: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/29629372/glomerular-endothelial-cells-stress-and-cross-talk-with-podocytes-in-the-development-of-diabetic-kidney-disease
#10
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
#11
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/29627526/role-of-akr1c3-in-renal-injury-and-glibenclamide-is-anti-inflammatory-in-preeclamptic-rats
#12
Cheng-Juan Sun, Ya Jin, Wei-Yuan Zhang, Lin Li, Xiao-Wei Liu
Proteinuria is a common adverse effect of renal injury in preeclampsia. To explore the effects of AKR1C3 in renal injury due to preeclampsia and to determine an optimal method to prevent proteinuria, glibenclamide treatment was used in unrestrained Wistar rats exposed to N-nitro-L-arginine methyl ester hydrochloride (L-NAME). Successful rat models for preeclampsia were confirmed based on mean arterial pressure, a 24-h protein urine test, and by observing the structure of the kidney by transmission electron microscopy (TEM)...
April 5, 2018: Gene
https://www.readbyqxmd.com/read/29621776/carnosine-catalyzes-the-formation-of-the-oligo-polymeric-products-of-methylglyoxal
#13
Tim Weigand, Benjamin Singler, Thomas Fleming, Peter Nawroth, Karel D Klika, Christian Thiel, Hans Baelde, Sven F Garbade, Andreas H Wagner, Markus Hecker, Benito A Yard, Albert Amberger, Johannes Zschocke, Claus P Schmitt, Verena Peters
BACKGROUND/AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MG), contribute to diabetic complications. MG-scavenging capacities of carnosine and anserine, which have been shown to mitigate diabetic nephropathy, were evaluated in vitro and in vivo. METHODS: MG-induced cell toxicity was characterized by MTT and MG-H1-formation, scavenging abilities by Western Blot and NMR spectroscopies, cellular carnosine transport by qPCR and microplate luminescence and carnosine concentration by HPLC...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29620171/tripterygium-glycoside-protects-against-puromycin-amino-nucleoside%C3%A2-induced-podocyte-injury-by-upregulating-autophagy
#14
Jianguang Gong, Juan Jin, Li Zhao, Yiqiao Li, Yiwen Li, Qiang He
Tripterygium glycoside (TG), an active ingredient of the widely used Chinese herb Tripterygium wilfordii Hook F, has immunosuppressive and anti‑inflammatory effects. Previous studies have indicated that TG is a potentially effective therapeutic option to treat nephrotic syndrome. The mechanism underlying the therapeutic effect of TG, including its effect on autophagy and apoptosis in podocyte injury, remains to be fully elucidated. The present study aimed to assess the protective effect of TG on podocytes via its potential role in the activation of autophagic and phosphatidylinositol 3‑kinase (PI3K) pathways...
March 29, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29619899/salvia-przewalskii-extract-of-total-phenolic-acids-inhibit-tlr4-signaling-activation-in-podocyte-injury-induced-by-puromycin-aminonucleoside-in-vitro
#15
Hongqi Ren, Xueqing Hu, Yun Liu, Deshu Dai, Xiang Liu, Zenghui Wang, Yang Yang, Xiangyang Li, Ying Liu, Renxian Tang
BACKGROUND: TLR4 signaling is known to be involved in podocyte injury. We have previously shown that Salvia przewalskii extract of total phenolic acids (SPE) and its active monomer salvianolic acid B (SalB) and rosmarinic acid (RA) protect podocytes from injury induced by PAN. In the present study, we test whether SPE inhibits TLR4 signaling. METHODS: The conditionally immortalized mouse podocytes were treated with SPE, SalB, RA, SalB + RA or tacrolimus for 30 min, followed by PAN (100 μg/mL) for 24 h...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29611334/conditional-ablation-of-the-prorenin-receptor-in-nephron-progenitor-cells-results-in-developmental-programming-of-hypertension
#16
Renfang Song, Laura Kidd, Adam Janssen, Ihor V Yosypiv
Nephron induction during kidney development is driven by reciprocal interactions between progenitor cells (NPCs) of the cap mesenchyme (CM) and the ureteric bud (UB). The prorenin receptor (PRR) is a receptor for renin and prorenin, and an accessory subunit of the vacuolar proton pump V-ATPase. Previously, we demonstrated that conditional ablation of the PRR in Six2+ NPCs in mice (Six2PRR -/- ) causes early neonatal death. Here, we identified genes that are regulated by PRR in Six2+ NPCs FACS-isolated from Six2PRR -/- and control kidneys on embryonic day E15...
April 2018: Physiological Reports
https://www.readbyqxmd.com/read/29608912/glomerular-mitochondrial-changes-in-hiv-associated-renal-injury
#17
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/29608407/epitope-mapping-of-monoclonal-antibody-pmab-48-against-dog-podoplanin
#18
Shinji Yamada, Mika K Kaneko, Shunsuke Itai, Yao-Wen Chang, Takuro Nakamura, Miyuki Yanaka, Satoshi Ogasawara, Takeshi Murata, Hiroaki Uchida, Hideaki Tahara, Hiroyuki Harada, Yukinari Kato
Podoplanin (PDPN), a type I transmembrane sialoglycoprotein, is expressed on normal renal podocytes, pulmonary type I alveolar cells, and lymphatic endothelial cells. Increased expression of PDPN in cancers is associated with poor prognosis and hematogenous metastasis through interactions with C-type lectin-like receptor 2 (CLEC-2) on platelets. We previously reported a novel PMab-48 antibody, which is an anti-dog PDPN (dPDPN) monoclonal antibody (mAb) recognizing PDPN expressed in lymphatic endothelial cells...
April 2, 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29604956/berberine-ameliorates-diabetic-nephropathy-by-inhibiting-tlr4-nf-%C3%AE%C2%BAb-pathway
#19
Liping Zhu, Jiakai Han, Rongrong Yuan, Lei Xue, Wuyan Pang
BACKGROUND: Diabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood. METHODS: The DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model...
March 31, 2018: Biological Research
https://www.readbyqxmd.com/read/29602834/nephrin-binding-ephrin-b1-at-the-slit-diaphragm-controls-podocyte-function-through-the-jnk-pathway
#20
Yoshiyasu Fukusumi, Ying Zhang, Ryohei Yamagishi, Kanako Oda, Toru Watanabe, Katsuyuki Matsui, Hiroshi Kawachi
Background B-type ephrins are membrane-bound proteins that maintain tissue function in several organs. We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear. Methods We analyzed the phenotype of podocyte-specific ephrin-B1 knockout mice and assessed the molecular association of ephrin-B1 and nephrin, a key molecule of the slit diaphragm, in HEK293 cells and rats with anti-nephrin antibody-induced nephropathy...
March 30, 2018: Journal of the American Society of Nephrology: JASN
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