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Proximal tubule

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https://www.readbyqxmd.com/read/29244860/lithium-reduces-blood-glucose-levels-but-aggravates-albuminuria-in-btbr-ob-ob-mice
#1
Theun de Groot, Lars Damen, Leanne Kosse, Mohammad Alsady, Rosalinda Doty, Ruben Baumgarten, Susan Sheehan, Johan van der Vlag, Ron Korstanje, Peter M T Deen
Glycogen synthase kinase 3 (GSK3) plays an important role in the development of diabetes mellitus and renal injury. GSK3 inhibition increases glucose uptake in insulin-insensitive muscle and adipose tissue, while it reduces albuminuria and glomerulosclerosis in acute kidney injury. The effect of chronic GSK3 inhibition in diabetic nephropathy is not known. We tested the effect of lithium, the only clinical GSK3 inhibitor, on the development of diabetes mellitus and kidney injury in a mouse model of diabetic nephropathy...
2017: PloS One
https://www.readbyqxmd.com/read/29241623/knockout-of-the-interleukin-36-receptor-protects-against-renal-ischemia-reperfusion-injury-by-reduction-of-proinflammatory-cytokines
#2
Hirofumi Nishikawa, Yoshinori Taniguchi, Tatsuki Matsumoto, Naoki Arima, Mamoru Masaki, Yoshiko Shimamura, Kosuke Inoue, Taro Horino, Shimpei Fujimoto, Kentaro Ohko, Toshihiro Komatsu, Keiko Udaka, Shigetoshi Sano, Yoshio Terada
IL-36, a newly named member of the IL-1 cytokine family, includes 3 isoforms, IL-36α, IL-36β, and IL-36γ, all of which bind to a heterodimer containing the IL-36 receptor (IL-36R). Little is known about the role of the IL-36 axis in acute kidney injury (AKI) pathogenesis. Therefore, we evaluated IL-36 function in the bilateral renal ischemia-reperfusion injury model of AKI using IL-36R knockout and wild-type mice. IL-36R was found to be expressed in the kidney, mainly in proximal tubules. In IL-36R knockout mice, plasma creatinine, blood urea nitrogen, and IL-6 levels after ischemia-reperfusion injury were significantly lower than those in wild-type mice...
December 11, 2017: Kidney International
https://www.readbyqxmd.com/read/29241374/pharmacokinetic-drug-evaluation-of-empagliflozin-plus-linagliptin-for-the-treatment-of-type-2-diabetes
#3
C V Rizos, T D Filippatos, M S Elisaf
Type 2 diabetes mellitus has become a growing epidemic and therefore efficient treatment strategies that target its management are needed. The treatment of diabetic patients often requires the combination of antidiabetic drug classes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) block glucose reabsorption in the proximal renal tubules. Dipeptidyl peptidase-4 inhibitors (DPP-4i) improve glucose metabolism by blocking the enzyme that degrades incretins leading to increased insulin secretion. Areas covered: The aim of the review is to present the available data on pharmacokinetic properties/pharmacodynamics, metabolic and cardiovascular effects...
December 15, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29240625/orbital-shear-stress-regulates-differentiation-and-barrier-function-of-primary-renal-tubular-epithelial-cells
#4
Nicholas Ferrell, Jin Cheng, Simeng Miao, Shuvo Roy, William H Fissell
Primary cells cultured in vitro gradually lose features characteristic of the in vivo phenotype. Culture techniques that help maintain cell-specific phenotype are advantageous for development of tissue engineered and bioartificial organs. Here we evaluated the phenotype of primary human renal tubule epithelial cells subjected to fluid shear stress by culturing the cells on an orbital shaker. Transepithelial electrical resistance (TEER), cell density, and gene and protein expression of proximal tubule-specific functional markers were measured in cells subjected to orbital shear stress...
December 11, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/29237739/salt-losing-tubulopathies-in-children-what-s-new-what-s-controversial
#5
Robert Kleta, Detlef Bockenhauer
Renal tubulopathies provide insights into the inner workings of the kidney, yet also pose therapeutic challenges. Because of the central nature of sodium in tubular transport physiology, disorders of sodium handling may affect virtually all aspects of the homeostatic functions of the kidney. Yet, owing to the rarity of these disorders, little clinical evidence regarding treatment exists. Consequently, treatment can vary widely between individual physicians and centers and is based mainly on understanding of renal physiology, reported clinical observations, and individual experiences...
December 13, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29236802/tadalafil-protector-effect-during-ischemia-reperfusion-in-rats
#6
Eduardo Gabriel Gerber Wietzikoski, Julio Cesar Foiatto, Nicolau Gregori Czeczko, Osvaldo Malafaia, Fernando Cesar Koleski, Tiago Cesar Mierzwa, Regina de Paula Xavier Gomes
PURPOSE: To evaluate histological parameters in rat renal tissue after tadalafil use during hot ischemia for 45 minutes and reperfusion for 24 hours. METHODS: Twenty rats were divided into 2 groups. In the experimental group 10 mg/kg of tadalafil was used per gavage before the procedure. All cases underwent left partial nephrectomy, followed by 45 minutes of warm ischemia. Left nephrectomy of the remaining kidney was performed after 24 hours from the initial procedure...
November 2017: Acta Cirúrgica Brasileira
https://www.readbyqxmd.com/read/29234448/aristolochic-acid-induced-autophagy-promotes-epithelial-to-myofibroblast-transition-in-human-renal-proximal-tubule-epithelial-cells
#7
Yu-Lin Man, Hong-Liang Rui, Yi-Pu Chen, Guo-Qin Wang, Li-Jun Sun, Hong Cheng
Autophagy plays an essential role in cellular homeostasis in kidney. Previous studies have found that aristolochic acid (AA) can induce autophagy of renal tubular epithelial cells and epithelial-to-myofibroblast transition (EMT). However, the relationship between AA-induced autophagy and EMT is unclear. Our results showed that, after AA stimulation, the appearance of autophagy preceded EMT. Autophagy of HKC cells began to increase gradually from the 3rd hour, reached the peak at 12th hour, and then weakened gradually until 36th hour; the EMT process of HKC continued to increase from 6th hour to 36th hour after AA stimulation...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29229234/trans-resveratrol-mitigates-type-1-diabetes-induced-oxidative-dna-damage-and-accumulation-of-advanced-glycation-end-products-in-glomeruli-and-tubules-of-rat-kidneys
#8
Heba Al-Hussaini, Narayana Kilarkaje
Hyperglycemia induces the formation of advanced glycation end products (AGEs) and their receptors (RAGEs), which alter several intracellular signaling mechanisms leading to the onset and progression of diabetic nephropathy. The present study focused on, i) modulatory effects of trans-resveratrol (3,5,4'-trihydroxy-trans-stilbene) on structural changes, AGE (NƐ-carboxymethyl-lysine), RAGE, oxidative stress and DNA damage, and apoptosis, and ii) localization of fibrotic changes, AGE, RAGE, 8-oxo-dG and 4-hydroxynonenal (4-HNE) in diabetic rat kidneys...
December 8, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29228653/overexpression-of-capn2-promotes-cell-metastasis-and-proliferation-via-akt-mtor-signaling-in-renal-cell-carcinoma
#9
Chenkui Miao, Chao Liang, Ye Tian, Aiming Xu, Jundong Zhu, Kai Zhao, Jianzhong Zhang, Yibo Hua, Shouyong Liu, Huiyu Dong, Chao Zhang, Shifeng Su, Pu Li, Chao Qin, Zengjun Wang
The calpain 2 (CAPN2) is upregulated in various malignant carcinomas. Previous studies have reported that CAPN2 functioned as an oncogenic factor in human cancers. However, its clinical role and potential effects on cell metastasis and proliferation in renal cell carcinoma (RCC) remain unknown. In this study, we evaluated the mRNA and protein levels of CAPN2 in human RCC specimens, matched normal specimens, and RCC cell lines using quantitative Real-time PCR (RT-PCR) and western blot. Immunohistochemistry of 74 RCC tissues in a tissue microarrays (TMAs) and normal kidney tissues were performed...
November 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29223554/oral-administration-of-nigella-sativa-oil-and-thymoquinone-attenuates-long-term-cisplatin-treatment-induced-toxicity-and-oxidative-damage-in-rat-kidney
#10
Zeba Farooqui, Faaiza Shahid, Aijaz Ahmed Khan, Farah Khan
Cisplatin (CP) is an effective anti-cancer drug which causes remarkable toxicity to the kidney, particularly to proximal tubules, by generating reactive oxygen species. Nigella sativa (NS), commonly known as "black cumin" reduces the progression of various kidney disorders. Thymoquinone (TQ), the major bioactive constituent of NS seeds, has been credited for various pharmacological effects of NS. Since, a typical clinical CP dosing regimen involves CP administration in multiple cycles over a long time duration, hence the present study aimed to evaluate the renoprotective efficacy of NS oil and TQ against multiple dose CP treatment induced deleterious biochemical and histological alterations in rat kidney...
December 6, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29218530/tracking-glut2-translocation-by-live-cell-imaging
#11
Sabina Tsytkin-Kirschenzweig, Merav Cohen, Yaakov Nahmias
The facilitative glucose transporter (GLUT) family plays a key role in metabolic homeostasis, controlling the absorption rates and rapid response to changing carbohydrate levels. The facilitative GLUT2 transporter is uniquely expressed in metabolic epithelial cells of the intestine, pancreas, liver, and kidney. GLUT2 dysfunction is associated with several pathologies, including Fanconi-Bickel syndrome, a glycogen storage disease, characterized by growth retardation and renal dysfunction. Interestingly, GLUT2 activity is modulated by its cellular localization...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29217627/the-gastric-caecum-of-larval-aedes-aegypti-stimulation-of-epithelial-ion-transport-by-5-hydroxytryptamine-and-camp
#12
Natalie M D'Silva, Michael J O'Donnell
We report measurements of ion transport across the gastric caecum of larvae of Aedes aegypti, a vector of yellow fever that inhabits a variety of aquatic habitats ranging from freshwater to brackish water. We provide the first measurements of the effect of 5-hydroxytryptamine (5-HT) on transepithelial potential (TEP), luminal ion concentrations and electrochemical potentials, as well as basolateral membrane potential and H+, Na+ and K+ fluxes. TEP, basolateral membrane potential, and H+, K+, and Na+ fluxes across the gastric caeca declined within 3-6 mins after isolation of the entire midgut from the larva...
December 7, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29217467/why-should-we-measure-free-25-oh-vitamin-d
#13
REVIEW
Oleg Tsuprykov, Xin Chen, Carl-Friedrich Hocher, LianghongYin, Berthold Hocher
Vitamin D, either in its D2 or D3 form, is essential for normal human development during intrauterine life, kidney function and bone health. Vitamin D deficiency has also been linked to cancer development and some autoimmune diseases. Given this huge impact of vitamin D on human health, it is important for daily clinical practice and clinical research to have reliable tools to judge on the vitamin D status. The major circulating form of vitamin D3 is 25-hydroxyvitamin D3 (25(OH)D), although is not the most active metabolite, the concentrations of total 25-hydroxy vitamin D3 in the serum are currently routinely used in clinical practice to assess vitamin D status...
December 4, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29215110/quercetin-inhibits-renal-cyst-growth-in-vitro-and-via-parenteral-injection-in-a-polycystic-kidney-disease-mouse-model
#14
Yangyang Zhu, Tian Teng, Hu Wang, Hao Guo, Lei Du, Baoxue Yang, Xiaoxing Yin, Ying Sun
Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disease characterized by massive enlargement of fluid-filled cysts in the kidney. There is an urgent need to develop effective ADPKD therapies. We used an in vitro Madin-Darby canine kidney (MDCK) cyst model and a murine embryonic kidney cyst model to evaluate whether quercetin inhibits cyst development. We then used a polycystic kidney disease (PKD) mouse model to further determine the in vivo effects of quercetin (100 mg per kg body weight twice per day) on PKD mice via subcutaneous injections...
December 7, 2017: Food & Function
https://www.readbyqxmd.com/read/29212764/aberrant-dna-methylation-of-pregnane-x-receptor-underlies-metabolic-gene-alterations-in-the-diabetic-kidney
#15
Atsushi Watanabe, Takeshi Marumo, Wakako Kawarazaki, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Kohei Ueda, Daigoro Hirohama, Toshiya Tanaka, Shintaro Yagi, Satoshi Ota, Genta Nagae, Hiroyuki Aburatani, Hiroo Kumagai, Toshiro Fujita
Epigenetic abnormalities have been suggested to mediate metabolic memory observed in diabetic complications. We have shown that epigenetic alterations may induce persistent phenotypic changes in the proximal tubules of the diabetic kidneys. In this study, we show that pregnane X receptor (PXR), a xenobiotic nuclear receptor, is epigenetically altered and upregulated, and may have a possible function in the diabetic kidney. PXR has been shown to play a critical role in metabolic changes in obesity and diabetes; however, its distribution and function in the kidney are unknown...
December 6, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29211853/nrf2-deficiency-upregulates-intrarenal-angiotensin-converting-enzyme-2-and-angiotensin-1-7-receptor-expression-and-attenuates-hypertension-and-nephropathy-in-diabetic-mice
#16
Shuiling Zhao, Anindya Ghosh, Chao-Sheng Lo, Isabelle Chenier, James W Scholey, Janos G Filep, Julie R Ingelfinger, Shao-Ling Zhang, John S D Chan
We investigated the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in renin-angiotensin system (RAS) gene expression in renal proximal tubule cells (RPTCs) and in the development of systemic hypertension and kidney injury in diabetic Akita mice. We used adult male Akita Nrf2 knockout (KO) mice and Akita mice treated with trigonelline (an Nrf2 inhibitor) or oltipraz (an Nrf2 activator). We also examined immortalized rat RPTCs (IRPTCs) stably transfected with control plasmids or plasmids containing rat angiotensinogen (Agt), angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (Ace2) or angiotensin 1-7 receptor (MasR) gene promoters...
December 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/29207627/orellanine-specifically-targets-renal-clear-cell-carcinoma
#17
Lisa Buvall, Heidi Hedman, Alina Khramova, Deman Najar, Lovisa Bergwall, Kerstin Ebefors, Carina Sihlbom, Sven Lundstam, Anders Herrmann, Hanna Wallentin, Emelie Roos, Ulf A Nilsson, Martin Johansson, Jan Törnell, Börje Haraldsson, Jenny Nyström
Renal cell carcinoma (RCC), arising from the proximal tubule in the kidney, accounts for approximately 85% of kidney cancers and causes over 140,000 annual deaths worldwide. In the last decade, several new therapies have been identified for treatment of metastatic RCC. Although these therapies increase survival time compared to standard care, none of them has curative properties. The nephrotoxin orellanine specifically targets proximal tubular epithelial cells, leaving other organs unaffected. We therefore hypothesized that the selective toxicity of orellanine extends to clear cell RCC (ccRCC) cells since they emanate from proximal tubular cells...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29205334/sodium-glucose-cotransporter-2-inhibitor-canagliflozin-attenuates-liver-cancer-cell-growth-and-angiogenic-activity-by-inhibiting-glucose-uptake
#18
Kosuke Kaji, Norihisa Nishimura, Kenichiro Seki, Shinya Sato, Soichiro Saikawa, Keisuke Nakanishi, Masanori Furukawa, Hideto Kawaratani, Mitsuteru Kitade, Kei Moriya, Tadashi Namisaki, Hitoshi Yoshiji
Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) comprise a new class of antidiabetic agents that inhibit glucose reabsorption in the renal proximal tubules. Although a recent report demonstrated the potential ability of SGLT2-Is to attenuate cancer growth of SGLT2-expressing cancer cells, little is known about the effects of SGLT2-Is on hepatocellular carcinoma (HCC). Here, we investigate the anti-cancer properties of a SGLT2-I, canagliflozin, against human liver cancer cells. SGTL2 mRNA and protein expression were detected in Huh7 and HepG2 cells, although not in HLE as well as primary human hepatocytes and hepatic stellate cells...
December 4, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29204517/proteomic-analysis-of-aqp11-null-kidney-proximal-tubular-type-polycystic-kidney-disease
#19
Tatsuya Saito, Yasuko Tanaka, Yoshiyuki Morishita, Kenichi Ishibashi
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by the mutation of polycystins (PC-1 or PC-2), in which cysts start from the collecting duct to extend to all nephron segments with eventual end stage renal failure. The cyst development is attenuated by a vasopressin V2 receptor antagonist tolvaptan which, however, will not affect proximal tubule cysts devoid of V2 receptor. Aquaporin-11 (AQP11) is expressed selectively in the proximal tubule of the kidney and AQP11-null kidneys have a disruptive PC-1 trafficking to the plasma membrane to develop polycystic kidneys...
March 2018: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29198839/sox9-activation-is-involved-in-tubule-repair-after-unilateral-partial-nephrectomy
#20
Qiwang Ma, Yujia Wang, Wei Zuo
AIMS: Tubule repair has been noticed after kidney tissue damage, however the cellular mechanism behind remains unclear. Here we successfully constructed a mouse unilateral partial nephrectomy model mimicking renal carcinoma surgery, and further investigated whether this procedure triggered regenerative action. MAIN METHODS: We used the unilateral partial nephrectomy model to study kidney repair. Kidney function after nephrectomy was measured using creatinine and urea nitrogen assay kit...
November 30, 2017: Life Sciences
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