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https://www.readbyqxmd.com/read/28714420/evaluation-of-temporal-changes-in-urine-based-metabolomic-and-kidney-injury-markers-to-detect-compound-induced-acute-kidney-tubular-toxicity-in-beagle-dogs
#1
M P Wagoner, Y Yang, J E McDuffie, M Klapczynski, W Buck, L Cheatham, D Eisinger, F Sace, K M Lynch, M Sonee, J-Y Ma, Y Chen, K Marshall, M Damour, L Stephen, Y P Dragan, J Fikes, S Snook, L B Kinter
Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute drug induced kidney injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin-induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urine-based metabolomic fingerprint...
July 13, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28699526/hydrogel-based-cell-therapies-for-kidney-regeneration-current-trends-in-biofabrication-and-in-vivo-repair
#2
Katja Jansen, Carl C L Schuurmans, Jitske Jansen, Rosalinde Masereeuw, Tina Vermonden
Facing the problems of limited renal regeneration capacity and the persistent shortage of donor kidneys, dialysis remains the only treatment option for many end-stage renal disease patients. Unfortunately, dialysis is only a medium-term solution because large and protein-bound uremic solutes are not efficiently cleared from the body and lead to disease progression over time. Current strategies for improved renal replacement therapies (RRTs) range from whole organ engineering to biofabrication of renal assist devices and biological injectables for in vivo regeneration...
July 10, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28688581/persistent-and-inducible-neogenesis-repopulates-progenitor-renin-lineage-cells-in-the-kidney
#3
Linda Hickmann, Anne Steglich, Michael Gerlach, Moath Al-Mekhlafi, Jan Sradnick, Peter Lachmann, Maria Luisa S Sequeira-Lopez, R Ariel Gomez, Bernd Hohenstein, Christian Hugo, Vladimir T Todorov
Renin lineage cells (RLCs) serve as a progenitor cell reservoir during nephrogenesis and after renal injury. The maintenance mechanisms of the RLC pool are still poorly understood. Since RLCs were also identified as a progenitor cell population in bone marrow we first considered that these may be their source in the kidney. However, transplantation experiments in adult mice demonstrated that bone marrow-derived cells do not give rise to RLCs in the kidney indicating their non-hematopoietic origin. Therefore we tested whether RLCs develop in the kidney through neogenesis (de novo differentiation) from cells that have never expressed renin before...
July 6, 2017: Kidney International
https://www.readbyqxmd.com/read/28620747/amniotic-fluid-cells-current-progress-and-emerging-challenges-in-renal-regeneration
#4
REVIEW
Stefano Da Sacco, Laura Perin, Sargis Sedrakyan
Amniotic fluid (AF) contains a heterogeneous population of cells that have been identified to possess pluripotent and progenitor-like characteristics. These cells have been applied in various regenerative medicine applications ranging from in vitro cell differentiation to tissue engineering to cellular therapies for different organs including the heart, the liver, the lung, and the kidneys. In this review, we examine the different methodologies used for the derivation of amniotic fluid stem cells and renal progenitors, and their application in renal repair and regeneration...
June 15, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28620603/advances-in-the-knowledge-about-kidney-decellularization-and-repopulation
#5
REVIEW
Afrânio Côgo Destefani, Gabriela Modenesi Sirtoli, Breno Valentim Nogueira
End-stage renal disease (ESRD) is characterized by the progressive deterioration of renal function that may compromise different tissues and organs. The major treatment indicated for patients with ESRD is kidney transplantation. However, the shortage of available organs, as well as the high rate of organ rejection, supports the need for new therapies. Thus, the implementation of tissue bioengineering to organ regeneration has emerged as an alternative to traditional organ transplantation. Decellularization of organs with chemical, physical, and/or biological agents generates natural scaffolds, which can serve as basis for tissue reconstruction...
2017: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/28612137/cross-talk-between-the-crumbs-complex-and-hippo-signaling-in-renal-epithelial-cells
#6
REVIEW
U Michgehl, H Pavenstädt, B Vollenbröker
Cell polarity has a crucial role in organizing cells into tissues and in mediating transport processes and cell-cell communication. Especially the cells of the nephron require apicobasal polarity to establish and maintain their barrier function. The Crumbs complex including the integral membrane protein Crumbs, as well as Pals1 and Patj, is essential for the establishment of apicobasal polarity. The interactions of the core proteins and the interplay with other processes have been characterized in various epithelial cell lines in detail...
June 13, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28587817/human-renal-tubular-cells-contain-cd24-cd133-progenitor-cell-populations-implications-for-tubular-regeneration-after-toxicant-induced-damage-using-cadmium-as-a-model
#7
Swojani Shrestha, Seema Somji, Donald A Sens, Andrea Slusser-Nore, Divyen H Patel, Evan Savage, Scott H Garrett
The proximal tubules of the kidney are target sites of injury by various toxicants. Cadmium (Cd(+2)), an environmental nephrotoxicant can cause adverse effects and overt renal damage. To decipher the mechanisms involved in nephrotoxicity, an in vitro model system is required. Mortal cultures of human proximal tubule (HPT) cells have served, as models but are difficult to acquire and do not lend themselves to stable transfection. The immortalized human proximal tubule cell line HK-2, has served as a model but it lacks vectorial active transport and shows signs of lost epithelial features...
June 3, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28566468/smad7-protects-against-acute-kidney-injury-by-rescuing-tubular-epithelial-cells-from-the-g1-cell-cycle-arrest
#8
Sha Fu, Ying Tang, Xiao R Huang, Min Feng, An P Xu, Hui Y Lan
Smad7 plays a protective role in chronic kidney disease; however, its role in acute kidney injury (AKI) remains unexplored. Here, we report that Smad7 protects against AKI by rescuing the G1 cell cycle arrest of tubular epithelial cells (TECs) in ischemia/reperfusion-induced AKI in mice in which Smad7 gene is disrupted or restored locally into the kidney. In Smad7 gene knockout (KO) mice, more severe renal impairment including higher levels of serum creatinine and massive tubular necrosis was developed at 48 h after AKI...
August 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28556588/effects-of-dna-methylation-on-progression-to-interstitial-fibrosis-and-tubular-atrophy-in-renal-allograft-biopsies-a-multi-omics-approach
#9
Sai Vineela Bontha, Daniel G Maluf, Kellie J Archer, Catherine I Dumur, Mikhail Dozmorov, Anne King, Enver Akalin, Thomas F Mueller, Lorenzo Gallon, Valeria R Mas
Progressive fibrosis of the interstitium is the dominant final pathway in renal destruction in native and transplanted kidneys. Over time, the continuum of molecular events following immunological and non-immunological insults lead to interstitial fibrosis and tubular atrophy (IFTA) and culminate in kidney failure. We hypothesize that these insults trigger changes in DNA methylation (DNAm) patterns which in turn could exacerbate injury and slow down the regeneration processes, leading to fibrosis development and graft dysfunction...
May 28, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28539339/mif-2-d-dt-enhances-proximal-tubular-cell-regeneration-through-slpi-and-atf4-dependent-mechanisms
#10
Akinobu Ochi, Dong Chen, Wibke Schulte, Lin Leng, Nickolas Gilbert Moeckel, Marta Piecychna, Luisa Averdunk, Christian Stoppe, Richard Bucala, Gilbert W Moeckel
Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic actions that is produced by several organs and cell types. Depending on the target cell and the inflammatory context, MIF can engage its two component receptor complex CD74 and CD44, and the chemokine receptors CXCR2/4. MIF is constitutively expressed in renal proximal tubular cells, stored in intracellular preformed pools and is released at a low rate. Recently a second MIF-like protein (i.e. MIF-2/D-DT) has been characterized in mammals...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28526628/heparin-based-hydrogels-induce-human-renal-tubulogenesis-in-vitro
#11
Heather M Weber, Mikhail V Tsurkan, Valentina Magno, Uwe Freudenberg, Carsten Werner
Dialysis or kidney transplantation is the only therapeutic option for end stage renal disease. Accordingly, there is a large unmet clinical need for new causative therapeutic treatments. Obtaining robust models that mimic the complex nature of the human kidney is a critical step in the development of new therapeutic strategies. Here we establish a synthetic in vitro human renal tubulogenesis model based on a tunable glycosaminoglycan-hydrogel platform. In this system, renal tubulogenesis can be modulated by the adjustment of hydrogel mechanics and degradability, growth factor signaling, and the presence of insoluble adhesion cues, potentially providing new insights for regenerative therapy...
May 17, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28513838/the-emerging-role-of-npnt-in-tissue-injury-repair-and-bone-homeostasis
#12
REVIEW
Youqiang Sun, Vincent Kuek, Heng Qiu, Jennifer Tickner, Leilei Chen, Haibin Wang, Wei He, Jiake Xu
Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an important role in regulating cell adhesion, differentiation, spreading and survival. NPNT protein belongs to epidermal growth factor (EGF)-like superfamily and exhibits several common structural determinants; including EGF-like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein-Tyrosine Phosphatase µ), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It regulates integrins-mediated signaling pathways via the interaction of its RGD motif with integrin α8β1...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28498963/hypertension-in-kidney-transplantation-is-associated-with-an-early-renal-nerve-sprouting
#13
Alessandro Mauriello, Valentina Rovella, Filippo Borri, Lucia Anemona, Elena Giannini, Erica Giacobbi, Andrea Saggini, Giampiero Palmieri, Alessandro Anselmo, Pierluigi Bove, Gerry Melino, Guardini Valentina, Manfredi Tesauro, D'Urso Gabriele, Nicola Di Daniele
Background.: Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney. Methods.: We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively...
June 1, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28471327/renal-regenerative-potential-of-different-extracellular-vesicle-populations-derived-from-bone-marrow-mesenchymal-stromal-cells
#14
Stefania Bruno, Marta Tapparo, Federica Collino, Giulia Chiabotto, Maria Chiara Deregibus, Rafael Soares Lindoso, Francesco Neri, Sharad Kholia, Sara Giunti, Sicheng Wen, Peter Quesenberry, Giovanni Camussi
Extracellular vesicles (EVs) derived from human bone marrow mesenchymal stromal cells (MSCs) promote the regeneration of kidneys in different animal models of acute kidney injury (AKI) in a manner comparable with the cells of origin. However, due to the heterogeneity observed in the EVs isolated from MSCs, it is unclear which population is responsible for the proregenerative effects. We therefore evaluated the effect of various EV populations separated by differential ultracentrifugation (10K population enriched with microvesicles and 100K population enriched with exosomes) on AKI recovery...
June 13, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28469775/melatonin-promoted-renal-regeneration-in-folic-acid-induced-acute-kidney-injury-via-inhibiting-nucleocytoplasmic-translocation-of-hmgb1-in-tubular-epithelial-cells
#15
Fengming Zhu, Octavia Ls Chong Lee Shin, Huzi Xu, Zhi Zhao, Guangchang Pei, Zhizhi Hu, Juan Yang, Yanchao Guo, Jingyi Mou, Jie Sun, Han Zhu, Yuxi Wang, Meng Wang, Qian Yang, Wenhui Liao, Gang Xu, Rui Zeng, Ying Yao
Melatonin (N-acetyl-5-methoxytryptamine), a circadian-regulating hormone, has been reported to exert a protective role during acute kidney injury (AKI) induced by renal ischemia-reperfusion injury (I/R). High-mobility group box 1 (HMGB1) is a novel member of the damage-associated molecular pattern (DAMP) family, and has been verified to be an inflammatory cytokine mediating AKI induced by I/R and cisplatin. However, the effect of melatonin on HMGB1, as well as the relationship of these two with folic acid induced AKI are elusive...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28466106/augmenter-of-liver-regeneration-regulates-autophagy-in-renal-ischemia-reperfusion-injury-via-the-ampk-mtor-pathway
#16
Tao Pu, Xiao-Hui Liao, Hang Sun, Hui Guo, Xiao Jiang, Jun-Bo Peng, Ling Zhang, Qi Liu
Autophagy may have protective effects in renal ischemia-reperfusion (I/R) injury, although the underlying mechanisms remain unclear. Augmenter of liver regeneration (ALR), a widely distributed multifunctional protein that is originally identified as a hepatic growth factor, may participate in the process of autophagy. To investigate the role of ALR in autophagy, ALR expression is knocked-down in human kidney 2 (HK-2) cells with short hairpin RNA lentivirals. Then, the level of autophagy is measured in the shRNA/ALR group and the shRNA/control group in an in vitro model of ischemia-reperfusion (I/R)...
July 2017: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/28454301/immunohistochemical-profile-of-ing3-protein-in-normal-and-cancerous-tissues
#17
Wen-Feng Gou, Xue-Feng Yang, Dao-Fu Shen, Shuang Zhao, Hong-Zhi Sun, Jun-Sheng Luo, Hua-Chuan Zheng
The inhibitor of growth family, member 3 (ING3) protein may be capable of blocking the cell cycle via activating p53-transactivated promoters of p21 and Bcl2-associated X protein, and may induce apoptosis via a Fas/caspase-8-dependent signaling pathway. In the present study, immunohistochemistry was performed in order to characterize the expression profile of ING3 protein in tissue microarrays containing mouse and human normal tissue, human hepatocellular (n=62), renal clear cell (n=62), pancreatic (n=62), esophageal squamous cell (n=45), cervical squamous cell (n=31), breast (n=144), gastric (n=196), colorectal (n=96), ovarian (n=208), endometrial (n=96) and lung carcinoma (n=192)...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28418911/elevated-serum-level-of-pancreatic-stone-protein-regenerating-protein-psp-reg-is-observed-in-diabetic-kidney-disease
#18
Ling Li, Dongyu Jia, Rolf Graf, Jiayue Yang
Diabetic kidney disease (DKD) is a major complication of diabetes, and serves as an important cause of end-stage renal disease (ESRD). The role of chronic inflammation in DKD is becoming widely accepted. Pancreatic stone protein/regenerating protein (PSP/reg) is a secretory protein, which is elevated in blood during infected conditions and organ failure. The aim of this study was to investigate the relationship between serum PSP/reg and DKD in patients with type 2 diabetes (T2DM). A total of 120 subjects which includes newly diagnosed T2DM patients, diabetes patients without DKD, DKD patients, as well as healthy controls were enrolled in this study...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416198/engineering-human-renal-epithelial-cells-for-transplantation-in-regenerative-medicine
#19
Vita Manzoli, David C Colter, Sridevi Dhanaraj, Alessia Fornoni, Camillo Ricordi, Antonello Pileggi, Alice A Tomei
Cellular transplantation may treat several human diseases by replacing damaged cells and/or providing a local source of trophic factors promoting regeneration. We utilized human renal epithelial cells (hRECs) isolated from cadaveric donors as a cell model. For efficacious implementation of hRECs for treatment of kidney diseases, we evaluated a novel encapsulation strategy for immunoisolation of hRECs and lentiviral transduction of the Green Fluorescent Protein (GFP) as model gene for genetic engineering of hRECs to secrete desired trophic factors...
April 13, 2017: Medical Engineering & Physics
https://www.readbyqxmd.com/read/28411024/epcam-controls-morphogenetic-programs-during-zebrafish-pronephros-development
#20
Sebastian Kuechlin, Maximilian Schoels, Krasimir Slanchev, Silke Lassmann, Gerd Walz, Toma A Yakulov
Epithelial cell adhesion molecule EpCAM is a transmembrane glycoprotein that is dynamically expressed in human and murine renal epithelia during development. The levels of EpCAM in the renal epithelium are upregulated both during regeneration after ischemia/reperfusion injury and in renal-derived carcinomas. The role of EpCAM in early kidney development, however, has remained unclear. The zebrafish pronephros shows a similar segmentation pattern to the mammalian metanephric nephron, and has recently emerged as a tractable model to study the regulatory programs governing early nephrogenesis...
April 12, 2017: Biochemical and Biophysical Research Communications
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