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https://www.readbyqxmd.com/read/29330945/cyclosporine-a-induces-endothelin-converting-enzyme-ece-1-studies-in-vivo-and-in-vitro
#1
Samuel N Heyman, Zaid Abassi, Christian Rosenberger, Hiba Yaseen, Galia Skarjinski, Ahuva Shina, Susanne Mathia, Natalia Krits, Mogher Khamaisi
AIM: Cyclosporine A (CsA) induces renal vasoconstriction and hypoxia and enhances the expression of endothelin-1 (ET-1) pro-hormone (pre-pro ET-1), plausibly leading to a feed-forward loop of renal vasoconstriction, hypoxia, and enhanced synthesis of the potent vasoconstrictor ET-1. Endothelin converting enzyme (ECE)-1 cleaves big endothelin to generate endothelin (ET)-1 and is up-regulated by hypoxia via hypoxia-inducible factor (HIF). We hypothesized that in addition to the direct induction of ET-1 synthesis, CsA might also intensify renal ECE-1expression, thus contributing to enhanced ET-1 synthesis following CsA...
January 13, 2018: Acta Physiologica
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/29240625/orbital-shear-stress-regulates-differentiation-and-barrier-function-of-primary-renal-tubular-epithelial-cells
#3
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/29212764/aberrant-dna-methylation-of-pregnane-x-receptor-underlies-metabolic-gene-alterations-in-the-diabetic-kidney
#4
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/29207633/camkii-is-involved-in-subcellular-ca2-redistribution-induced-endoplasmic-reticulum-stress-leading-to-apoptosis-in-primary-cultures-of-rat-proximal-tubular-cells-exposed-to-lead
#5
Min-Ge Wang, Wen-Hui Li, Xin-Yu Wang, Du-Bao Yang, Zhen-Yong Wang, Lin Wang
Lead (Pb) is a known nephrotoxic element. Recently we have proved that subcellular Ca2+ redistribution is involved in Pb-induced apoptosis in primary cultures of rat proximal tubular (rPT) cells, but the underlying mechanism remains to be elucidated. Firstly, data showed that Pb triggers endoplasmic reticulum (ER) stress response in rPT cells, as evidenced by the elevations of ER stress markers. Moreover, pharmacological modulation of Ca2+ mobilization in ER and cytoplasm with three chemicals (2-APB or TG or BAPTA-AM) can effectively increase or decrease the protein expression of ER stress markers in Pb-exposed rPT cells, demonstrating that Pb-induced ER stress is Ca2+-dependent...
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
#6
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/29197217/rptec-tert1-cells-form-highly-differentiated-tubules-when-cultured-in-a-3d-matrix
#7
Philipp F Secker, Lisanne Luks, Nadja Schlichenmaier, Daniel R Dietrich
The proximal tubule is the primary site for renal solute reabsorption and secretion and thus a main target for drug-induced toxicity. Current nonclinical methods using 2D cell cultures are unable to fully recapitulate clinical drug responses mainly due to limited in vitro functional lifespan. Since extracellular matrices are known to be key regulators of cell development, culturing cells on classic 2D plastic surfaces inevitably results in loss of differentiation. Hence, 3D models of the human proximal tubule that recapitulate the in vivo morphology would allow for improved drug screening and disease modeling...
December 2, 2017: ALTEX
https://www.readbyqxmd.com/read/29187371/effects-of-erythropoietin-receptor-activity-on-angiogenesis-tubular-injury-and-fibrosis-in-acute-kidney-injury-a-u-shaped-relationship
#8
Mingjun Shi, Brianna Flores, Peng Li, Nancy Gillings, Kathryn L McMillan, Jianfeng Ye, Lily June-Shen Huang, Sachdev S Sidhu, Yong-Ping Zhong, Maria T Grompe, Philip R Streeter, Orson W Moe, Ming Chang Hu
Erythropoietin receptor (EpoR) is widely expressed but its renoprotective action is unexplored. To examine the role of EpoR in vivo in the kidney, we induced acute kidney injury (AKI) by ischemia-reperfusion in mice with different EpoR bioactivities in the kidney. EpoR bioactivity was reduced by knock-in of wild type human EpoR, which is hypo-functional relative to murine EpoR, and a renal tubule-specific EpoR knockout. These mice had lower EPO/EpoR activity and lower autophagy flux in renal tubules. Upon AKI induction, they exhibited worse renal function and structural damage, and more apoptosis at the acute stage (< 7 days), and slower recovery with more tubulointerstitial fibrosis at the subacute stage (14 days)...
November 29, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29158549/hypoxia-inducible-factor-1%C3%AE-mediates-the-profibrotic-effect-of-albumin-in-renal-tubular-cells
#9
Junping Hu, Weili Wang, Fan Zhang, Pin-Lan Li, Krishna M Boini, Fan Yi, Ningjun Li
Proteinuria is closely associated with the progression of chronic kidney diseases (CKD) by producing renal tubulointerstitial fibrosis. Over-activation of hypoxia inducible factor (HIF)-1α has been implicated in the progression of CKD. The present study tested the hypothesis that HIF-1α mediates albumin-induced profibrotic effect in cultured renal proximal tubular cells. Incubation of the cells with albumin (40 μg/ml) for 72 hrs significantly increased the protein levels of HIF-1α, tissue inhibitor of metalloproteinase (TIMP)-1 and collagen-I, which were blocked by HIF-1α shRNA...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29124787/reduced-tubular-degradation-of-glomerular-filtered-plasma-albumin-is-a-common-feature-in-acute-and-chronic-kidney-disease
#10
Yingjie Han, Nguyen D K Ly, Greg H Tesch, Philip Poronnik, David J Nikolic-Paterson
Tubular epithelial cells take up and degrade plasma albumin filtered by the glomerulus. Tubular damage resulting in reduced albumin uptake or degradation has been suggested as one mechanism contributing to albuminuria in kidney disease. This study investigated whether tubular albumin uptake or degradation is altered in acute and chronic glomerular disease. Mouse models of acute glomerular injury (anti-GBM disease and LPS-induced albuminuria) and chronic disease (streptozotocin-induced diabetes and db/db mice) were examined...
November 10, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/29109726/il-36%C3%AE-regulates-tubulointerstitial-inflammation-in-the-mouse-kidney
#11
Osamu Ichii, Junpei Kimura, Tadashi Okamura, Taro Horino, Teppei Nakamura, Hayato Sasaki, Yaser Hosny Ali Elewa, Yasuhiro Kon
IL-36α, a member of the IL-1 family, is a crucial mediator of inflammatory responses. We previously found that IL-36α was overexpressed in injured distal tubules (DTs); however, its pathological function remains unclear. Herein, unilateral ureter obstruction (UUO) or folic acid (FA) injection was performed in mouse kidneys to assess the role of IL-36α in kidney injury. IL-36α mRNA and protein expression significantly increased in the kidneys within 24 h after UUO. IL-36α localized to dilated DTs. IL-36α expression significantly correlated with the progression of tubulointerstitial cell infiltration and tubular epithelium cell death in UUO kidneys and with renal dysfunction in FA-induced acute kidney injury mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29106063/cannabinoid-1-receptor-deletion-in-podocytes-mitigates-both-glomerular-and-tubular-dysfunction-in-a-mouse-model-of-diabetic-nephropathy
#12
Tony Jourdan, Joshua K Park, Zoltán V Varga, János Pálóczi, Nathan J Coffey, Avi Z Rosenberg, Grzegorz Godlewski, Resat Cinar, Ken Mackie, Pal Pacher, George Kunos
AIMS: To determine the specific role of podocyte-expressed cannabinoid-1 receptor (CB1 R) in the development of diabetic nephropathy (DN), relative to CB1 R in other renal cell types. MATERIAL AND METHODS: We developed a mouse model with a podocyte-specific deletion of CB1 R (pCB1Rko) and challenged this model with streptozotocin (STZ)-induced type-1 DN. We also assessed the podocyte response to high glucose in vitro and its effects on CB1 R activation. RESULTS: High glucose exposure for 48h led to an increase in CB1 R gene expression (CNR1) and endocannabinoid production in cultured human podocytes...
November 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29065889/injury-induced-expression-of-caveolar-proteins-in-human-kidney-tubules-role-of-megakaryoblastic-leukemia-1
#13
Krzysztof M Krawczyk, Jennifer Hansson, Helén Nilsson, Katarzyna K Krawczyk, Karl Swärd, Martin E Johansson
BACKGROUND: Caveolae are membrane invaginations measuring 50-100 nm. These organelles, composed of caveolin and cavin proteins, are important for cellular signaling and survival. Caveolae play incompletely defined roles in human kidneys. Induction of caveolin-1/CAV1 in diseased tubules has been described previously, but the responsible mechanism remains to be defined. METHODS: Healthy and atrophying human kidneys were stained for caveolar proteins, (caveolin 1-3 and cavin 1-4) and examined by electron microscopy...
October 24, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/29042455/microrna-709-mediates-acute-tubular-injury-through-effects-on-mitochondrial-function
#14
Yan Guo, Jiajia Ni, Shuang Chen, Mi Bai, Jiajuan Lin, Guixia Ding, Yue Zhang, Pingping Sun, Zhanjun Jia, Songming Huang, Li Yang, Aihua Zhang
Mitochondrial dysfunction has important roles in the pathogenesis of AKI, yet therapeutic approaches to improve mitochondrial function remain limited. In this study, we investigated the pathogenic role of microRNA-709 (miR-709) in mediating mitochondrial impairment and tubular cell death in AKI. In a cisplatin-induced AKI mouse model and in biopsy samples of human AKI kidney tissue, miR-709 was significantly upregulated in the proximal tubular cells (PTCs). The expression of miR-709 in the renal PTCs of patients with AKI correlated with the severity of kidney injury...
October 17, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29037855/nephrosphere-derived-cells-are-induced-to-multilineage-differentiation-when-cultured-on-human-decellularized-kidney-scaffolds
#15
Silvia Bombelli, Chiara Meregalli, Carla Scalia, Giorgio Bovo, Barbara Torsello, Sofia De Marco, Massimiliano Cadamuro, Paolo Viganò, Guido Strada, Giorgio Cattoretti, Cristina Bianchi, Roberto A Perego
In end-stage chronic kidney disease, the option of organ transplantation is limited because of the scarce availability of kidneys. The combination of stem cell research, regenerative medicine, and tissue engineering seems a promising approach to produce new transplantable kidneys. Currently, the possibility to repopulate naturally obtained scaffolds with cells of different sources is advancing. Our aim was to test, for the first time, whether the nephrosphere (NS) cells, composed by renal stem/progenitor-like cells, were able to repopulate different nephron portions of renal extracellular matrix scaffolds obtained after decellularization of human renal tissue slices...
October 14, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/29032370/an-immunofluorescence-assay-for-extracellular-matrix-components-highlights-the-role-of-epithelial-cells-in-producing-a-stable-fibrillar-extracellular-matrix
#16
Omar S Qureshi, Hélène Bon, Breda Twomey, Gill Holdsworth, Kirsty Ford, Marianne Bergin, Linghong Huang, Mariusz Muzylak, Louise J Healy, Vanessa Hurdowar, Timothy S Johnson
Activated fibroblasts are considered major drivers of fibrotic disease progression through the production of excessive extracellular matrix (ECM) in response to signals from damaged epithelial and inflammatory cells. Nevertheless, epithelial cells are capable of expressing components of the ECM, cross-linking enzymes that increase its stability and are sensitive to factors involved in the early stages of fibrosis. We therefore wanted to test the hypothesis that epithelial cells can deposit ECM in response to stimulation in a comparable manner to fibroblasts...
October 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28994737/anti-inflammatory-pyranochalcone-derivative-attenuates-lps-induced-acute-kidney-injury-via-inhibiting-tlr4-nf-%C3%AE%C2%BAb-pathway
#17
Min Shi, Xiaoxi Zeng, Fan Guo, Rongshuang Huang, Yanhuan Feng, Liang Ma, Li Zhou, Ping Fu
Treatment of septic acute kidney injury (AKI) has still been beyond satisfaction, although anti-inflammatory therapy is beneficial for sepsis-induced AKI. Compound 5b was derived from natural pyranochalcones and exhibited potent anti-inflammatory activity in adjuvant-induced arthritis. In this study, we aimed to investigate the renoprotective effects and potential mechanism of 5b against lipopolysaccharide (LPS)-induced AKI. C57BL/6 mice and human renal proximal tubule cell line (HK-2 cell) were treated with LPS, respectively...
October 10, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28993506/kidney-proximal-tubule-lipoapoptosis-is-regulated-by-fatty-acid-transporter-2-fatp2
#18
Shenaz Khan, Pablo D Cabral, William P Schilling, Zachary W Schmidt, Asif N Uddin, Amelia Gingras, Sethu M Madhavan, Jeffrey L Garvin, Jeffrey R Schelling
Albuminuria and tubular atrophy are among the highest risks for CKD progression to ESRD. A parsimonious mechanism involves leakage of albumin-bound nonesterified fatty acids (NEFAs) across the damaged glomerular filtration barrier and subsequent reabsorption by the downstream proximal tubule, causing lipoapoptosis. We sought to identify the apical proximal tubule transporter that mediates NEFA uptake and cytotoxicity. We observed transporter-mediated uptake of fluorescently labeled NEFA in cultured proximal tubule cells and microperfused rat proximal tubules, with greater uptake from the apical surface than from the basolateral surface...
October 9, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28990525/a-human-proximal-tubular-epithelial-cell-model-to-explore-a-knowledge-gap-on-neonatal-drug-disposition
#19
Ahmed Reda, Anke Raaijmakers, Saskia van Dorst, Charlotte G G M Pauwels, Karel Allegaert, Mohamed A Elmonem, Rosalinde Masereeuw, Lambertus van den Heuvel, Elena Levtchenko, Fanny Oliveira Arcolino
BACKGROUND: Finding the right drug-dosage for neonates is still a challenge. Until now, neonatal doses are extrapolated from adults and children doses. However, there are differences between neonatal and adult kidney physiology that should be considered, especially when it comes to drug metabolism and/or transport. Studying renal drug disposition in neonates is limited by the lack of reliable human cell models. OBJECTIVE: To illustrate the feasibility of developing an in vitro model for neonatal proximal tubule epithelial cells (nPTECs) to study renal drug disposition at this age...
October 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28979210/chronic-hypobaric-hypoxia-modulates-primary-cilia-differently-in-adult-and-fetal-ovine-kidneys
#20
Kiumars Shamloo, Juan Chen, Jasmine Sardar, Rinzhin T Sherpa, Rajasekharreddy Pala, Kimberly F Atkinson, William J Pearce, Lubo Zhang, Surya M Nauli
Hypoxic environments at high altitude have significant effects on kidney injury. Following injury, renal primary cilia display length alterations. Primary cilia are mechanosensory organelles that regulate tubular architecture. The effect of hypoxia on cilia length is still controversial in cultured cells, and no corresponding in vivo study exists. Using fetal and adult sheep, we here study the effect of chronic hypobaric hypoxia on the renal injury, intracellular calcium signaling and the relationship between cilia length and cilia function...
2017: Frontiers in Physiology
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