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Renal proximal tubule

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https://www.readbyqxmd.com/read/29784932/molecular-size-modulates-pharmacokinetics-biodistribution-and-renal-deposition-of-the-drug-delivery-biopolymer-elastin-like-polypeptide
#1
Marija Kuna, Fakhri Mahdi, Alejandro R Chade, Gene L Bidwell
Elastin-like polypeptides (ELP) are engineered proteins that consist of repetitions of a five amino acid motif, and their composition is easily modified to adjust their physical properties and attach therapeutics. Because of the repetitive nature of the ELP sequence, polymer size is particularly amenable to manipulation. ELP fusion proteins are being actively developed as therapeutics for many disease applications, and how the ELP size and shape affects its pharmacokinetics and biodistribution is a critical question for the general field of ELP drug delivery...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29783804/-acquired-cystic-kidney-disease-associated-renal-cell-carcinoma-a-clinicopathologic-study-of-three-cases
#2
W Zhang, L L Xu, W J Yu, Q Wang, Y X Jiang, Y Liu, Y J Li
Objective: To study the clinicopathologic, immunohistochemical (IHC), histogenetic and prognostic features of acquired cystic kidney disease-associated renal cell carcinoma (ACKD-RCC). Methods: Three cases of ACKD-RCC, including two from 401 Hospital of PLA and one from the Affiliated Hospital of Qingdao University were studied by clinical, histological and IHC analysis with review of relevant literature. Results: All the three patients were male, ranging from 46 to 78 years old. All patients had history of chronic renal failure; two patients were treated with hemodialysis for 9 years and 11 years, respectively...
May 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
https://www.readbyqxmd.com/read/29782346/claudins-and-nephrolithiasis
#3
Allein Plain, R Todd Alexander
PURPOSE OF REVIEW: The greatest risk factor for kidney stone formation is increased urinary calcium excretion. Most filtered calcium is reabsorbed from the proximal tubule and the thick ascending limb (TAL) of Henle's loop via a paracellular pathway. Claudins are tight junction proteins that confer the permeability properties of an epithelium. We review the contribution of renal claudins to nephron calcium permeability and how perturbations in these pathways cause alterations in tubular calcium transport, hypercalciuria, nephrocalcinosis, or nephrolithiasis...
May 17, 2018: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/29781318/hypochlorite-modified-albumins-promote-cell-death-in-the-tubule-interstitium-in-rats-via-mitochondrial-damage-in-obstructive-nephropathy-and-the-protective-effects-of-antioxidant-peptides
#4
Zong-Rui Liu, Si-Qi Chen, Yao-Wei Zou, Xiao-Yu Wu, Hong-Ying Li, Xiao-Qiao Wang, Yue Shi, Hong-Xin Niu
A major feature of the injury sustained by the kidney during obstructive nephropathy is a profound induction of apoptosis in the tubular epithelium. In this study, we explored the central roles of mitochondria and the mechanism of the protective effect of the mitochondrial targeted peptides in tubular cell apoptosis and interstitial fibrosis during obstructive nephropathy. Unilateral ureter obstruction (UUO) was performed on rats, and the animals were randomly assigned to intravenous treatment with normal saline, rat serum albumin (RSA), or HOCl-rat serum albumin (HOCl-RSA) in the presence or absence of SS-31...
May 2018: Free Radical Research
https://www.readbyqxmd.com/read/29773167/optimal-dosage-and-early-intervention-of-l-ascorbic-acid-inhibiting-k-2-cr-2-o-7-induced-renal-tubular-cell-damage
#5
Tzeng-Jih Lin, Yeou-Lih Huang, Jung-San Chang, Kuan-Ting Liu, Meng-Chi Yen, Fen-Wei Chen, Yueh-Lun Shih, Jo-Chi Jao, Po-Chi Huang, I-Jeng Yeh
Chromium poisoning can cause renal failure and death. Chromium intoxication may be managed using L-ascorbic acid (vitamin C) therapy. However, the evidence supporting the effectiveness of this treatment is insufficient, and the mechanism of action has not been clarified in renal cells. In this study, our results showed that the optimal regimen of L-ascorbic acid therapy in human epithelial renal proximal tubule cells, HK-2 cells, was 30 μg/mL. Supplementation of L-ascorbic acid with 30 μg/mL and within 8 h of chromium intoxication (K2 Cr2 O7, Cr6+ ) was effective to inhibit renal tubular cell damage by blocking generation of free radicals, cell apoptosis, and autophagy...
July 2018: Journal of Trace Elements in Medicine and Biology
https://www.readbyqxmd.com/read/29772789/downregulation-of-the-s1p-transporter-spinster-homology-protein-2-spns2-exerts-an-anti-fibrotic-and-anti-inflammatory-effect-in-human-renal-proximal-tubular-epithelial-cells
#6
Olivier Blanchard, Bisera Stepanovska, Manuel Starck, Martin Erhardt, Isolde Römer, Dagmar Meyer Zu Heringdorf, Josef Pfeilschifter, Uwe Zangemeister-Wittke, Andrea Huwiler
Sphingosine kinase (SK) catalyses the formation of sphingosine 1-phosphate (S1P), which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ) induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF) and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29769449/fatty-acid-receptor-modulator-pbi-4050-inhibits-kidney-fibrosis-and-improves-glycemic-control
#7
Yan Li, Sungjin Chung, Zhilian Li, Jessica M Overstreet, Lyne Gagnon, Brigitte Grouix, Martin Leduc, Pierre Laurin, Ming-Zhi Zhang, Raymond C Harris
Extensive kidney fibrosis occurs in several types of chronic kidney diseases. PBI-4050, a potentially novel first-in-class orally active low-molecular weight compound, has antifibrotic and antiinflammatory properties. We examined whether PBI-4050 affected the progression of diabetic nephropathy (DN) in a mouse model of accelerated type 2 diabetes and in a model of selective tubulointerstitial fibrosis. eNOS-/- db/db mice were treated with PBI-4050 from 8-20 weeks of age (early treatment) or from 16-24 weeks of age (late treatment)...
May 17, 2018: JCI Insight
https://www.readbyqxmd.com/read/29768670/patients-affected-by-a-new-variant-of-endemic-pemphigus-foliaceus-have-autoantibodies-colocalizing-with-myzap-p0071-desmoplakins-1-2-and-arvcf-causing-renal-damage
#8
A M Abreu-Velez, M S Howard, H Yi, A A Florez-Vargas
BACKGROUND: We have previously reported that about 30% of patients affected by a new variant of endemic pemphigus foliaceus (EPF) in El Bagre, Colombia (termed El Bagre-EPF or pemphigus Abreu-Manu) have systemic compromise. In the current study, we focused on studying autoreactivity to the kidney and its pathological correlations. AIM: To investigate patients with El Bagre-EPF for renal compromise. METHODS: We performed a case-control study, enrolling 57 patients with El Bagre-EPF and 57 controls from the endemic area, matched by age, sex, race, work activity, demographics and comorbidities...
May 16, 2018: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/29767557/polycystin-1-dysfunction-impairs-electrolyte-and-water-handling-in-a-renal-pre-cystic-mouse-model-for-adpkd
#9
Eric H J Verschuren, Sami G Mohammed, Wouter N Leonhard, Caro Overmars-Bos, Kimberly A M Veraar, Joost G J Hoenderop, René J M Bindels, Dorien J M Peters, Francisco J Arjona
The PKD1 gene encodes polycystin-1 (PC1), a mechanosensor triggering intracellular responses upon urinary flow sensing in kidney tubular cells. Mutations in PKD1 lead to autosomal dominant polycystic kidney disease (ADPKD). The involvement of PC1 in renal electrolyte handling remains unknown since renal electrolyte physiology in ADPKD patients has only been characterized in cystic ADPKD. We thus studied the renal electrolyte handling in inducible kidney-specific Pkd1 knockout (iKsp-Pkd1-/-) mice manifesting a pre-cystic phenotype...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29760122/perturbations-in-mitochondrial-dynamics-by-p66shc-lead-to-renal-tubular-oxidative-injury-in-human-diabetic-nephropathy
#10
Ming Zhan, Irtaza Usman, Jingbo Yu, Liemin Ruan, Xueyan Bian, Jun Yang, Shikun Yang, Lin Sun, Yashpal S Kanwar
Renal tubular injury is increasingly being recognized as an early characteristic of diabetic nephropathy (DN). Mitochondrial dynamic alterations and redox protein p66Shc-mediated oxidative stress are both critical for ensuing diabetic tubular cell injury and apoptosis; whether these two processes are interlinked remains unclear. In this study, we observed changes in mitochondrial morphology and expression of associated proteins in tubules of patients with DN. We demonstrated mitochondrial fragmentation as an important pathogenic feature of tubular cell injury that is linked to oxidative stress and p66Shc up-regulation...
May 14, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29750422/knockdown-of-snhg15-suppresses-renal-cell-carcinoma-proliferation-and-emt-by-regulating-the-nf-%C3%AE%C2%BAb-signaling-pathway
#11
Yang Du, Chuize Kong, Yuyan Zhu, Meng Yu, Zeliang Li, Jianbin Bi, Zhenhua Li, Xiankui Liu, Zhe Zhang, Xiuyue Yu
Aberrant expression of long noncoding RNAs (lncRNAs) is associated with cancer tumorigenesis and progression. It has been suggested that lncRNAs may be potential clinical diagnostic and prognostic biomarkers, and therapeutic targets. In the present study, the expression levels of small nucleolar RNA host gene 15 (SNHG15) were significantly upregulated in renal cell carcinoma (RCC) tissues and cell lines compared with in adjacent tissues and a proximal tubule epithelial cell line, as determined by reverse transcription‑quantitative polymerase chain reaction...
May 4, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29749806/rapamycin-induced-autophagy-protects-proximal-tubular-renal-cells-against-proteinuric-damage-through-the-transcriptional-activation-of-the-nerve-growth-factor-receptor-ngfr
#12
D Vizza, A Perri, G Toteda, S Lupinacci, I Perrotta, D Lofaro, F Leone, P Gigliotti, A La Russa, R Bonofiglio
Experimental evidence demonstrated that macroautophagy/autophagy exerts a crucial role in maintain renal cellular homeostasis and represents a protective mechanism against renal injuries. Interestingly, it has been demonstrated that in the human proximal tubular renal cell line, HK-2, the MTOR inhibitor rapamycin enhanced autophagy and mitigated the apoptosis damage induced by urinary protein overload. However, the underlying molecular mechanism has not yet been elucidated. In our study we demonstrated, for the first time, that in HK-2 cells, the exposure to low doses of rapamycin transactivated the NGFR promoter, leading to autophagic activation...
May 11, 2018: Autophagy
https://www.readbyqxmd.com/read/29745818/novel-insights-into-renal-mineralization-and-stone-formation-through-advanced-imaging-modalities
#13
Scott V Wiener, Ling Chen, Alex R Shimotake, Misun Kang, Marshall L Stoller, Sunita P Ho
Purpose/Aim: The most common kidney stone composed of calcium oxalate forms on interstitial calcium phosphate mineral known as a Randall's plaque (RP). Due to limited information about events leading to the initial deposition of nanometer size interstitial calcium phosphate pre-clusters, there continues to be a debate on the initial site of calcium phosphate deposition and factors leading to stone formation. MATERIALS AND METHODS: High-resolution X-ray micro-computed tomography (CT), and light and electron microscopy techniques were used to characterize human renal pyramids and five representative kidney stones with identifiable stems...
December 2018: Connective Tissue Research
https://www.readbyqxmd.com/read/29744639/drug-transporter-expression-profiling-in-a-three-dimensional-kidney-proximal-tubule-in-vitro-nephrotoxicity-model
#14
Dorina Diekjürgen, David W Grainger
Given currently poor toxicity translational predictions for drug candidates, improved mechanistic understanding underlying nephrotoxicity and drug renal clearance is needed to improve drug development and safety screening. Therefore, better relevant and well-characterized in vitro screening models are required to reliably predict human nephrotoxicity. Because kidney proximal tubules are central to active drug uptake and secretion processes and therefore to nephrotoxicity, this study acquired regio-specific expression data from recently reported primary proximal tubule three-dimensional (3D) hyaluronic acid gel culture and non-gel embedded cultured murine proximal tubule suspensions used in nephrotoxicity assays...
May 9, 2018: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/29731819/cytoprotective-effect-of-aquaporin-1-against-lipopolysaccharide-induced-apoptosis-and-inflammation-of-renal-epithelial-hk-2-cells
#15
Yiduo Wang, Wenzheng Zhang, Guangzhe Yu, Qian Liu, Yingyu Jin
Sepsis is the most common underlying disease of disseminated intravascular coagulation. Acute kidney injury is a common and serious complications of sepsis. In the present study, a lipopolysaccharide (LPS)-induced human proximal tubule cell line (HK-2 cells) was selected as an in vitro model of septic acute kidney injury. The aim of the present study was to investigate whether aquaporin 1 (AQP-1) has a cytoprotective role in LPS-induced HK-2 cells. HK-2 cells were treated with 0-16 µg/ml LPS for 0-24 h to establish the in vitro model of sepsis...
May 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29724319/-clinicopathological-features-and-treatment-of-renal-impair-in-primary-sj%C3%A3-gren-syndrome
#16
Jing Wang, Li Meng Chen
Primary Sjögren syndrome,characterized by autoimmune epithelitis,is a prevalent systemic autoimmune disease involving multiple organs,among which kidney is a major target organ.Tubulointerstitial lesion is the most frequent form,involving proximal tubule,distal tubule,or collecting duct.The disease has an occult onset and may progressively develop into renal function impairment and end-stage renal disease,which can be accompanied with low-molecular-weight proteinuria,renal tubule acidosis and electrolyte disturbance...
April 28, 2018: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/29720573/parabiosis-and-single-cell-rna-sequencing-reveal-a-limited-contribution-of-monocytes-to-myofibroblasts-in-kidney-fibrosis
#17
Rafael Kramann, Flavia Machado, Haojia Wu, Tetsuro Kusaba, Konrad Hoeft, Rebekka K Schneider, Benjamin D Humphreys
Fibrosis is the common final pathway of virtually all chronic injury to the kidney. While it is well accepted that myofibroblasts are the scar-producing cells in the kidney, their cellular origin is still hotly debated. The relative contribution of proximal tubular epithelium and circulating cells, including mesenchymal stem cells, macrophages, and fibrocytes, to the myofibroblast pool remains highly controversial. Using inducible genetic fate tracing of proximal tubular epithelium, we confirm that the proximal tubule does not contribute to the myofibroblast pool...
May 3, 2018: JCI Insight
https://www.readbyqxmd.com/read/29717935/expression-of-soluble-epoxide-hydrolase-in-renal-tubular-epithelial-cells-regulates-macrophage-infiltration-and-polarization-in-iga-nephropathy
#18
Qian Wang, Yan Liang, Yingjin Qiao, Xiangya Zhao, Yi Yang, Shengnan Yang, Bing Li, Qianru Zhao, Ling Dong, Songxia Quan, Rui Tian, Zhangsuo Liu
Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in kidney remains unknown...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29717156/high-basolateral-glucose-increases-sodium-glucose-cotransporter-2-and-reduces-sirtuin-1-in-renal-tubules-through-glucose-transporter-2-detection
#19
Hiroyuki Umino, Kazuhiro Hasegawa, Hitoshi Minakuchi, Hirokazu Muraoka, Takahisa Kawaguchi, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh
Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+ -dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29700792/preventive-effect-of-shenkang-injection-against-high-glucose-induced-senescence-of-renal-tubular-cells
#20
Biqiong Fu, Jie Yang, Jia Chen, Lirong Lin, Kehong Chen, Weiwei Zhang, Jianguo Zhang, Yani He
Shenkang injection (SKI) is a classic prescription composed of Radix Astragali, rhubarb, Astragalus, Safflower, and Salvia. This treatment was approved by the State Food and Drug Administration of China in 1999 for treatment of chronic kidney diseases based on good efficacy and safety. This study aimed to investigate the protective effect of SKI against high glucose (HG)-induced renal tubular cell senescence and its underlying mechanism. Primary renal proximal tubule epithelial cells were cultured in (1) control medium (control group), medium containing 5 mmol/L glucose; (2) mannitol medium (mannitol group), medium containing 5 mmol/L glucose, and 25 mmol/L mannitol; (3) HG medium (HG group) containing 30 mmol/L glucose; (4) SKI treatment at high (200 mg/L), medium (100 mg/L), or low (50 mg/L) concentration in HG medium (HG + SKI group); or (5) 200 mg/L SKI treatment in control medium (control + SKI group) for 72 h...
April 25, 2018: Frontiers of Medicine
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