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Renal proximal tubule

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https://www.readbyqxmd.com/read/28431667/the-potential-and-pitfalls-of-glp-1-receptor-agonists-for-renal-protection-in-type-2-diabetes
#1
Merlin C Thomas
Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) offer substantial benefits for the management of glucose levels in type 2 diabetes. In addition, recent data from clinical trials have demonstrated that treatment with Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RA) are also able to reduce new onset macroalbuminuria. These benefits may be consistent with the known effects of GLP-1 RA on traditional risk factors for progressive kidney disease including glucose lowering, blood pressure lowering, reduced insulin levels and weight reduction...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28428931/the-role-of-renal-proximal-tubule-transport-in-the-regulation-of-blood-pressure
#2
REVIEW
Shoko Horita, Motonobu Nakamura, Masashi Suzuki, Nobuhiko Satoh, Atsushi Suzuki, Yukio Homma, Masaomi Nangaku
The electrogenic sodium/bicarbonate cotransporter 1 (NBCe1) on the basolateral side of the renal proximal tubule plays a pivotal role in systemic acid-base homeostasis. Mutations in the gene encoding NBCe1 cause severe proximal renal tubular acidosis accompanied by other extrarenal symptoms. The proximal tubule reabsorbs most of the sodium filtered in the glomerulus, contributing to the regulation of plasma volume and blood pressure. NBCe1 and other sodium transporters in the proximal tubule are regulated by hormones, such as angiotensin II and insulin...
March 2017: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/28424212/pdgf-receptor-%C3%AE-uses-akt-mtorc1-signaling-node-to-promote-high-glucose-induced-renal-proximal-tubular-cell-collagen-i-%C3%AE-2-expression
#3
Falguni Das, Nandini Ghosh-Choudhury, Balachandar Venkatesan, Balakuntalam S Kasinath, Goutam Ghosh Choudhury
Increased expression of PDGF receptor-β (PDGFRβ) has been shown in the diabetic renal proximal tubules. The core molecular network used by high glucose to induce proximal tubular epithelial cell collagen I (α2) expression is poorly understood. We hypothesized that activation of PDGFRβ by high glucose increases collagen I (α2) production via Akt/mTORC1 signaling pathway in proximal tubular epithelial cells. Using biochemical and molecular biological techniques, we investigated this hypothesis. We show that high glucose increases activating phosphorylation of the PDGFRβ, resulting in the phosphorylation of the phosphatidylinositol 3 kinase...
April 19, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28417217/levels-of-cystatin-c-in-low-and-high-flux-hemodialysis-in-children-with-end-stage-renal-disease
#4
Fatina I Fadel, Abbass A Mourad, Azza M O Abdel Rahman, Hafez M Bazaraa, Mohamed Farouk Mohamed, Dalia H El-Lebedy, Mohamed M Soliman
BACKGROUND: Cystatin-C (CyC) is a middle molecule that is freely filtered at the glomerulus and almost completely reabsorbed by the proximal tubules. The aim of this study was to evaluate serum CyC and its reduction ratio as a biomarker for assessing the adequacy of the hemodialysis (HD) sessions in children with end-stage renal disease on maintenance HD. We also compared levels of CyC in patients on low-flux HD (LFH) and high-flux HD (HFH). METHODS: Forty patients were included in the study and divided into two groups, with one group (16 patients) receiving HFH and the other group receiving LFH (24 patients) (high-flux and low-flux polysulfone filters, respectively)...
April 17, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28408636/aldosterone-regulates-a-5-variant-sgk1-transcript-via-a-shared-hormone-response-element-in-the-sgk1-5-regulatory-region
#5
Nandita S Raikwar, Christie P Thomas
We previously identified a 5' variant alternate transcript of Sgk1 (Sgk1_v3) encoding an NH2-terminal variant Sgk1 isoform, Sgk1_i3 that, like Sgk1, is expressed in the distal convoluted tubule, connecting tubule and collecting duct and can stimulate epithelial Na(+) transport (Am J Physiol Renal Physiol 303: F1527-F1533, 2012). We now demonstrate that, similar to Sgk1, aldosterone and glucocorticoids stimulate Sgk1_v3 expression in cell lines from the collecting duct and airway epithelia. In mice, short term aldosterone infusion and maneuvers that increase endogenous aldosterone secretion including dietary Na(+) deprivation and K(+) loading increases distal nephron Sgk1_v3 expression in vivo...
April 2017: Physiological Reports
https://www.readbyqxmd.com/read/28404591/intravital-imaging-of-the-kidney-in-a-rat-model-of-salt-sensitive-hypertension
#6
Bradley T Endres, Ruben M Sandoval, George J Rhodes, Silvia B Campos-Bilderback, Malgorzata M Kamocka, Christopher McDermott-Roe, Alexander Staruschenko, Bruce A Molitoris, Aron M Geurts, Oleg Palygin
Hypertension is one of the most prevalent diseases worldwide, and a major risk factor for renal failure and cardiovascular disease. The role of albuminuria, a common feature of hypertension and robust predictor of cardiorenal disorders, remains incompletely understood. The goal of this study was to investigate the mechanisms leading to albuminuria in the kidney of a rat model of hypertension, the Dahl salt-sensitive (SS) rat. To determine the relative contributions of the glomerulus and proximal tubule (PT) to albuminuria, we applied intravital two-photon-based imaging to investigate the complex renal physiological changes that occur during salt-induced hypertension...
April 12, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28403692/severe-hypokalemia-due-to-a-possible-drug-drug-interaction-between-vinblastine-and-antiretrovirals-in-a-hiv-infected-patient-with-hodgkin-s-lymphoma
#7
Ezequiel Cordova, Laura Morganti, Andrea Odzak, Florencia Arcondo, Mariana Silva, Marcelo Zylberman, Claudia Rodriguez
A 60-year-old HIV-1 infected woman on antiretroviral therapy (emtricitabine/tenofovir, and ritonavir-boosted atazanavir) developed Hodgkin's lymphoma. The patient initiated ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) chemotherapy and presented with neutropenia and severe hypokalemia. Hypokalemia was considered as part of a proximal tubular renal dysfunction, and other causes of hypokalemia were excluded. Due to suspicion of drug--drug interactions between antiretrovirals and vinblastine, ritonavir-boosted atazanavir was switched to dolutegravir and the patient continued emtricitabine/tenofovir...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28401035/development-and-application-of-human-renal-proximal-tubule-epithelial-cells-for-assessment-of-compound-toxicity
#8
Shuaizhang Li, Jinghua Zhao, Ruili Huang, Toni Steiner, Maureen Bourner, Michael Mitchell, David C Thompson, Bin Zhao, Menghang Xia
Kidney toxicity is a major problem both in drug development and clinical settings. It is difficult to predict nephrotoxicity in part because of the lack of appropriate in vitro cell models, limited endpoints, and the observation that the activity of membrane transporters which plays important roles in nephrotoxicity by affecting the pharmacokinetic profile of drugs is often not taken into account. We developed a new cell model using pseudo-immortalized human primary renal proximal tubule epithelial cells. This cell line (SA7K) was characterized by the presence of proximal tubule cell markers as well as several functional properties, including transporter activity and response to a few well-characterized nephrotoxicants...
2017: Current Chemical Genomics and Translational Medicine
https://www.readbyqxmd.com/read/28400046/atgl-gene-deletion-predisposes-to-proximal-tubule-damage-by-impairing-the-fatty-acid-metabolism
#9
Wen Chen, Qiong Zhang, Shiwu Cheng, Jie Huang, Ge Diao, Jian Han
Fibrosis is the final common pathway of chronic kidney disease (CKD). Normal lipid metabolism is integral to renal physiology, and disturbances of renal lipid metabolism are increasingly being linked with CKD, including the fibrosis. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme of lipolysis. In the present study, we used Atgl(-/-) mice to investigate whether ATGL played a role in the regulation of proximal convoluted tubule (PCT) lipid metabolism and renal fibrosis development. ATGL deficiency led to lipid vacuolation of PCT and tubulointerstitial fibrosis, accompanied by massive albuminuria and decreased creatinine clearance rate (Ccr)...
April 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28395656/citrate-shows-protective-effects-on-cardiovascular-and-renal-function-in-ischemia-induced-acute-kidney-injury
#10
Anja Bienholz, Jonas Reis, Pinar Sanli, Herbert de Groot, Frank Petrat, Hana Guberina, Benjamin Wilde, Oliver Witzke, Fuat H Saner, Andreas Kribben, Joel M Weinberg, Thorsten Feldkamp
BACKGROUND: Ischemia and reperfusion (I/R) is one of the major causes of acute kidney injury (AKI). Citrate reduces hypoxia-induced mitochondrial energetic deficits in isolated proximal tubules. Moreover, citrate anticoagulation is now frequently used in renal replacement therapy. In the present study a rat model of I/R-induced AKI was utilized to examine renal protection by citrate in vivo. METHODS: AKI was induced by bilateral renal clamping (40 min) followed by reperfusion (3 h)...
April 10, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28395333/ovine-uterine-space-restriction-causes-dysregulation-of-the-renin-angiotensin-system-in-fetal-kidneys%C3%A2
#11
Rachel A Kranch-Shorthouse, Adam S Bauer, Ronald R Magness, Gladys E Lopez, Jeffrey L Segar, Sharon E Blohowiak, Pamela J Kling
In ovine pregnancy, uterine space restriction (USR) resulting from decreased space for placental attachment caused intrauterine growth restriction and impaired nephrogenesis. The fetal kidney renin-angiotensin system (RAS) is involved in nephrogenesis, fluid balance, and iron deposition. Angiotensin II exerts its effects via multiple receptors: angiotensin II 1-8 receptor type 1 (AT 1 R) and type 2 (AT 2 R), and angiotensin II 1-7 Mas receptor (MASR). Objective: : To test the hypothesis that ovine USR is associated with dysregulation of the fetal renal RAS...
January 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28391584/the-effect-of-ppar%C3%AE-agonist-on-sglt2-and-glucagon-expressions-in-alpha-cells-under-hyperglycemia
#12
M Kim, E J Lee, H M Shin, H S Jung, T K Kim, T N Kim, M J Kwon, S H Lee, B D Rhee, J H Park
BACKGROUND: Although sodium glucose cotransporter 2 (SGLT2) inhibitors have many beneficial effects for type 2 diabetes, including decreased cardiovascular death, recent reports that they increased glucagon through SGLT2 inhibition raised some concern. Troglitazone, Peroxisome proliferator-activated receptor γ (PPAR-γ) agonist, was reported to increase SGLT2 in renal proximal tubule cells, but its role on pancreatic alpha cells have not been reported. We investigated the effect of troglitazone on SGLT2 expression in alpha cells and subsequent glucagon regulation in hyperglycemia...
April 8, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28390812/characterization-of-pancreatic-islet-cell-tumors-and-renal-tumors-induced-by-a-combined-treatment-of-streptozotocin-and-nicotinamide-in-male-sd-rats
#13
Yuki Kato, Koichi Masuno, Kae Fujisawa, Noriko Tsuchiya, Mikinori Torii, Atsuko Hishikawa, Takeshi Izawa, Mitsuru Kuwamura, Jyoji Yamate
We herein investigated the histopathological features, including proliferative activity and immunoexpression, of pancreatic islet cell tumors (ICTs) in male SD rats induced by streptozotocin (STZ) and nicotinamide (NA), and discussed their relevance to biological behaviors and prognoses. A total of 70 and 43% of rats developed ICTs 37-45 weeks after the treatment with STZ (50 or 75mg/kg, i.v.) and NA (350mg/kg, twice, p.o.), respectively. Among the islet tumors observed in the STZ/NA-treated groups, 75% were adenomas, while 25% were carcinomas...
April 5, 2017: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/28387228/calcium-oxalate-crystals-and-oxalate-induce-an-epithelial-to-mesenchymal-transition-in-the-proximal-tubular-epithelial-cells-contribution-to-oxalate-kidney-injury
#14
Marcia Bastos Convento, Edson Andrade Pessoa, Edgar Cruz, Maria Aparecida da Glória, Nestor Schor, Fernanda Teixeira Borges
TGF-β1 is the main mediator of epithelial-to-mesenchymal transition (EMT). Hyperoxaluria induces crystalluria, interstitial fibrosis, and progressive renal failure. This study analyzed whether hyperoxaluria is associated with TGF-β1 production and kidney fibrosis in mice and if oxalate or calcium oxalate (CaOx) could induce EMT in proximal tubule cells (HK2) and therefore contribute to the fibrotic process. Hyperoxaluria was induced by adding hydroxyproline and ethylene glycol to the mice's drinking water for up to 60 days...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385546/cellular-uptake-of-levocetirizine-by-organic-anion-transporter-4
#15
Saki Noguchi, Tomohiro Nishimura, Saya Mukaida, Leslie Z Benet, Emi Nakashima, Masatoshi Tomi
The pharmacokinetics of cetirizine, a non-sedating antihistamine, is profoundly affected by transporter-mediated membrane transport in the kidney. In this study, we aimed to investigate the transport mechanism of levocetirizine, the pharmacologically active enantiomer of cetirizine, via human organic anion transporter 4 (OAT4) expressed in the apical membrane of renal proximal tubules and the basal plasma membrane of placental syncytiotrophoblasts. In cells expressing human OAT4 under the control of tetracycline, levocetirizine uptake was increased by tetracycline treatment...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28361319/making-a-kidney-organoid-using-the-directed-differentiation-of-human-pluripotent-stem-cells
#16
Minoru Takasato, Melissa H Little
An organoid can be defined as a three-dimensional organ-like structure formed from organ-specific progenitor cells. Organ progenitor cells were empirically found to self-organize three-dimensional tissues when they were aggregated and cultivated in vitro. While this nature power of progenitor cells has an amazing potential to recreate artificial organs in vitro, there had been difficulty to apply this technology to human organs due to the inaccessibility to human progenitor cells until human-induced pluripotent stem cell (hiPSC) was invented by Takahashi and Yamanaka in 2007...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28359809/wnt8a-expands-the-pool-of-embryonic-kidney-progenitors-in-zebrafish
#17
Richard W Naylor, Hwa In Han, Neil A Hukriede, Alan J Davidson
During zebrafish embryogenesis the pronephric kidney arises from a small population of posterior mesoderm cells that then undergo expansion during early stages of renal organogenesis. While wnt8 is required for posterior mesoderm formation during gastrulation, it is also transiently expressed in the post-gastrula embryo in the intermediate mesoderm, the precursor to the pronephros and some blood/vascular lineages. Here, we show that knockdown of wnt8a, using a low dose of morpholino that does not disrupt early mesoderm patterning, reduces the number of kidney and blood cells...
March 27, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28356293/urinary-dcr2-is-a-novel-biomarker-for-tubulointerstitial-injury-in-patients-with-diabetic-nephropathy
#18
Jia Chen, Wei-Wei Zhang, Ke-Hong Chen, Li-Rong Lin, Huan-Zi Dai, Kai-Long Li, Jian-Guo Zhang, Lu-Quan Zheng, Bi-Qiong Fu, Ya-Ni He
Tubulointerstitial injury (TII) plays a crucial role in the progression of diabetic nephropathy (DN), but lack of specific and sensitive biomarkers for monitoring TII in DN management. This study is to investigate whether urinary decoy receptor 2 (uDcR2) could serve as a novel noninvasive biomarker for assessing TII in DN. We recruited 311 type 2 diabetics and 139 DN patients which diagnosed by renal biopsy. uDcR2 levels were measured by ELISA and renal DcR2 expression was detected immunohistochemically. Associations between uDcR2 and renal DcR2, renal functional parameters were evaluated...
March 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28356267/hemoglobin-inhibits-albumin-uptake-by-proximal-tubule-cells-implications-for-sickle-cell-disease
#19
Megan L Eshbach, Amandeep Kaur, Youssef Rbaibi, Jesus Tejero, Ora A Weisz
Proximal tubule (PT) dysfunction, including tubular proteinuria, is a significant complication in young sickle cell disease (SCD) that can eventually lead to chronic kidney disease. Hemoglobin (Hb) dimers released from red blood cells upon hemolysis are filtered into the kidney and internalized by megalin/cubilin receptors into PT cells. The PT is especially sensitive to heme toxicity, and tubular dysfunction in SCD is thought to result from prolonged exposure to filtered Hb. Here we show that concentrations of Hb predicted to enter the tubule lumen during hemolytic crisis competitively inhibit the uptake of another megalin/cubilin ligand (albumin) by proximal tubule (PT) cells...
March 29, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28350099/small-heterodimer-partner-attenuates-hydrogen-peroxide-induced-expression-of-cyclooxygenase-2-and-inducible-nitric-oxide-synthase-by-suppression-of-activator-protein-1-and-nuclear-factor-%C3%AE%C2%BAb-in-renal-proximal-tubule-epithelial-cells
#20
Jung Sun Park, Hoon In Choi, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim
The orphan nuclear receptor, small heterodimer partner (SHP), plays a negative regulatory role in innate immune responses and is involved in various inflammatory signaling pathways. In the present study, we aimed to ascertain whether SHP is effective in preventing hydrogen peroxide (H2O2)-induced kidney tubular inflammation and explored the molecular mechanisms underlying the protective effects of SHP. Renal ischemia/reperfusion (I/R) injury was induced in mice by clamping both renal pedicles for 30 min...
February 9, 2017: International Journal of Molecular Medicine
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