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protein and AKI

Aki Hayashi, Katsunori Tanaka
The CRISPR/Cas9 system enables the editing of genomes of numerous organisms through the induction of the double-strand breaks (DSB) at specific chromosomal targets. We improved the CRISPR/Cas9 system to ease the direct introduction of a point mutation or a tagging sequence into the chromosome by combining it with the noncanonical homology-directed DNA repair (HDR) based genome editing in fission yeast. We constructed convenient cloning vectors, which possessed a guide RNA (gRNA) expression module, or the humanized Streptococcus pyogenes Cas9 gene that is expressed under the control of an inducible promoter to avoid the needless expression, or both a gRNA and Cas9 gene...
February 12, 2019: G3: Genes—Genomes—Genetics
Sina Waldherr, Alexander Fichtner, Bernd Beedgen, Thomas Bruckner, Franz Schaefer, Burkhard Tönshoff, Johannes Pöschl, Timm H Westhoff, Jens H Westhoff
BACKGROUND: Serum creatinine (SCr)- or urine output-based definitions of acute kidney injury (AKI) have important limitations in neonates. This study evaluates the diagnostic value of urinary biomarkers in very low-birth-weight (VLBW) infants receiving indomethacin for closure of a patent ductus arteriosus (PDA). METHODS: Prospective cohort study in 14 indomethacin-treated VLBW infants and 18 VLBW infants without indomethacin as controls. Urinary biomarkers were measured before, during, and after indomethacin administration...
February 11, 2019: Pediatric Research
Risto O Juvonen, Filip Novák, Eleni Emmanouilidou, Seppo Auriola, Juri Timonen, Aki T Heikkinen, Jenni Küblbeck, Moshe Finel, Hannu Raunio
Scoparone, a major constituent of the Chinese herbal medicine Yin Chen Hao, expresses beneficial effects in experimental models of various diseases. The intrinsic doses and effects of scoparone are dependent on its metabolism, both in humans and animals. We evaluated in detail the metabolism of scoparone in human, mouse, rat, pig, dog, and rabbit liver microsomes in vitro and in humans in vivo . Oxidation of scoparone to isoscopoletin via 6-O-demethylation was the major metabolic pathway in liver microsomes from humans, mouse, rat, pig and dog, whereas 7-O-demethylation to scopoletin was the main reaction in rabbit...
February 8, 2019: Planta Medica
Daisuke Ogasawara, Taka-Aki Ichu, Hui Jing, Jonathan J Hulce, Alex Reed, Olesya A Ulanovskaya, Benjamin F Cravatt
ABHD12 is a membrane-bound hydrolytic enzyme that acts on the lysophosphatidylserine (lyso-PS) and lysophosphatidylinositol (lyso-PI) classes of immunomodulatory lipids. Human and mouse genetic studies point to a key role for the ABHD12-(lyso)-PS/PI pathway in regulating (neuro)immunological functions in both the central nervous system and periphery. Selective inhibitors of ABHD12 would offer valuable pharmacological probes to complement genetic models of ABHD12-regulated (lyso)-PS/PI metabolism and signaling...
February 5, 2019: Journal of Medicinal Chemistry
Antonin Trimaille, Benjamin Marchandot, Mélanie Girardey, Clotilde Muller, Han S Lim, Annie Trinh, Patrick Ohlmann, Bruno Moulin, Laurence Jesel, Olivier Morel
BACKGROUND: Whereas the major strength of the simplified pulmonary embolism severity index (sPESI) lies in ruling out an adverse outcome in patients with sPESI of 0, the accuracy of sPESI ≥ 1 in risk assessment remains questionable. In acute pulmonary embolism (APE), the estimated glomerular filtration rate (eGFR) can be viewed as an integrate marker reflecting not only previous chronic kidney disease (CKD) damage but also comorbid conditions and hemodynamic disturbances associated with APE...
February 1, 2019: Journal of Clinical Medicine
Robert B Cameron, Whitney S Gibbs, Siennah R Miller, Tess V Dupre, Judit K Megyesi, Craig Cano Beeson, Rick G Schnellmann
Acute kidney injury (AKI) is the rapid loss of renal function following an insult and renal proximal tubule cells (RPTC) are central to the pathogenesis of AKI. The β2 adrenergic receptor (β2AR) agonist formoterol accelerates recovery of renal function in mice following ischemia-reperfusion injury (IRI) with associated rescue of mitochondrial proteins. However, the cell type responsible for this recovery remains unknown. The role of RPTC in formoterol-induced recovery of renal function was assessed in a proximal tubule-specific knockout of the β2AR (γGT-Cre:ADRB2Flox/Flox)...
February 1, 2019: Journal of Pharmacology and Experimental Therapeutics
Ou Li, Qian Ma, Fei Li, Guang-Yan Cai, Xiang-Mei Chen, Quan Hong
OBJECTIVE: Small ubiquitin-related modifiers (SUMOs) are a group of post-translational modification proteins extensively expressed in eukaryotes. Abnormal SUMOylation can lead to the development of various diseases. This article summarizes the progress on research of the role of SUMOs in various types of kidney diseases to further increase the understanding of the regulatory functions of SUMOylation in the pathogenesis of kidney diseases. DATA SOURCES: This review was based on articles published in the PubMed databases up to January 2018, using the keywords including "SUMOs," "SUMOylation," and "kidney diseases...
January 30, 2019: Chinese Medical Journal
David Zahler, Keren-Lee Rozenfeld, Maya Stein, Assi Milwidsky, Shlomo Berliner, Shmuel Banai, Yaron Arbel, Yacov Shacham
BACKGROUND: Elevated C-reactive protein (CRP) was shown to be associated with an increased risk for acute kidney injury (AKI) in ST elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI), however, the optimal time frame to measure CRP for risk stratification is not known. We evaluated the relation between the change in CRP over time (CRP velocity-CRPv) and AKI among STEMI patients treated with primary PCI. METHODS: We included 801 STEMI who presented between 2007 and 2017 and had their CRP measured with a wide range assay (wr-CRP) at least twice during the 24 h after admission...
January 31, 2019: Journal of Nephrology
Yang Zhang, Ling Wang, Lei Meng, Guangke Cao, Yu Wu
Sirtuin 6 (SIRT6) has the function of regulating autophagy. The aim of this study was to investigate the mechanism through which SIRT6 relieved acute kidney injury (AKI) caused by sepsis. The AKI model was established with lipopolysaccharides (LPS) using mice. Hematoxylin-eosin (HE) staining and streptavidin-perosidase (SP) staining was used to observe kidney tissue and test SIRT6 and LC3B proteins in kidney. Enzyme-linked immunosorbent assay (ELISA) was performed to detected the tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) concentrations...
January 30, 2019: Cell Cycle
Richard A Zager, Ali Cm Johnson
P21, a cyclin kinase inhibitor, is acutely up-regulated during AKI and exerts cytoprotective effects. A proposed mechanism is oxidant stress- induced activation of p53, the dominant p21 transcription factor. Glycerol-induced rhabdomyolysis induces profound renal oxidant stress. Hence, we studied this AKI model to determine whether p53 activation corresponds with p21 gene induction, and/or whether alternative mechanism(s) might be involved. CD-1 mice were subjected to glycerol-induced AKI. Either 4 or 18 hrs later, plasma, urinary, and renal cortical p21 protein and mRNA levels were assessed...
January 30, 2019: American Journal of Physiology. Renal Physiology
Liping Wang, Ning Liu, Xiaoyan Xue, Shujun Zhou
BACKGROUND Acute kidney injury (AKI) involves the renal tubular epithelium. The enhancer of zeste homolog 1 (EZH1) gene has a role in cell development and differentiation. This study aimed to investigate the effect of overexpression of the EZH1 gene on aristolochic acid-induced injury in HK-2 human kidney proximal tubule epithelial cells in vitro. MATERIAL AND METHODS The HK-2 cells were cultured and treated with aristolochic acid and the effects of aristolochic acid-injury were evaluated using a cell counting kit-8 (CCK-8) assay...
January 28, 2019: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Manuel Meurer, Klaus Höcherl
Fibroblast growth factor 23 (FGF23) levels are elevated in patients with acute kidney injury (AKI). The consequences on renal Ca2+ , Mg2+ , and Pi regulatory mechanisms are unknown. We hypothesized that renal ischemia-reperfusion (I/R) injury alters the expression of important renal Ca2+ , Mg2+ , and Pi transport proteins. I/R injury was induced in male C57BL/6 mice by clamping both renal arteries for 27 min. Mice were investigated 18 h later. The mRNA and protein levels of renal Ca2+ , Mg2+ , and Pi transport proteins were measured by RT-qPCR and western blot analysis...
January 26, 2019: Pflügers Archiv: European Journal of Physiology
Jieru Cai, Xiaoyan Jiao, Shuan Zhao, Yiran Liang, Yichun Ning, Yiqin Shi, Yi Fang, Xiaoqiang Ding, Xiaofang Yu
BACKGROUND: Regulatory T cells (Tregs) suppress excessive immune responses and play a crucial protective role in acute kidney injury (AKI). The aim of this study was to examine the therapeutic potential of transforming growth factor (TGF)-β1-overexpressing mesenchymal stromal cells (MSCs) in inducing local generation of Tregs in the kidney after ischemia/reperfusion (I/R) injury. METHODS: MSCs were transduced with a lentiviral vector expressing the TGF-β1 gene; TGF-β1-overexpressing MSCs (designated TGF-β1/MSCs) were then transfused into the I/R-injured kidney via the renal artery...
January 23, 2019: Cytotherapy
Xinghan Tian, Yongqiang Ji, Yafeng Liang, Jing Zhang, Lina Guan, Chunting Wang
BACKGROUND: Acute kidney injury (AKI) shows several kinds of disorders, which acutely harm the kidney. However, the current medical methods have limited therapeutic effects. The present study aimed to find out the molecular mechanism of AKI pathogenesis, which may provide new insights for future therapy. METHODS: Bioinformatic analysis was conducted using the R language (AT&T BellLaboratories, University of Auckland, New Zealand) to acquire the differentially expressed long noncoding RNAs (lncRNAs) and messenger RNAs (mRNAs) in AKI...
January 26, 2019: Journal of Cellular Physiology
Andrew J MacDonald, Mitra K Nadim, François Durand, Constantine J Karvellas
PURPOSE OF REVIEW: Acute kidney injury (AKI) in cirrhosis consists of varying phenotypes, with hepatorenal syndrome (HRS) representing a single entity. Prompt recognition and diagnosis of AKI cause identifies appropriate therapeutic measures. This review provides an overview of AKI definitions, highlights challenges in quantifying renal impairment in cirrhosis, lists novel diagnostic AKI biomarkers, and summarizes transplantation implications. RECENT FINDINGS: Biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18, and liver-type fatty acid-binding protein) may assist in the identification of underlying acute tubular necrosis...
January 22, 2019: Current Opinion in Critical Care
Jing Ji, Xiaoshuang Zhou, Ping Xu, Yafeng Li, Honglin Shi, Dexi Chen, Rongshan Li, Hongbo Shi
Acute kidney injury (AKI) has become a common disorder with a high risk of morbidity and mortality, which remains major medical problem without reliable and effective therapeutic intervention. Apoptosis-stimulating protein two of p53 (ASPP2) is a proapoptotic member that belongs to p53 binding protein family, which plays a key role in regulating apoptosis and cell growth. However, the role of ASPP2 in AKI has not been reported. To explore the role of ASPP2 in the progression of AKI, we prepared an AKI mouse model induced by ischaemia reperfusion (I/R) in wild-type (ASPP2+/+ ) mice and ASPP2 haploinsufficient (ASPP2+/- ) mice...
January 23, 2019: Journal of Cellular and Molecular Medicine
Naomi Tanga, Kazuya Kuboyama, Ayako Kishimoto, Hiroshi Kiyonari, Aki Shiraishi, Ryoko Suzuki, Toshio Watanabe, Akihiro Fujikawa, Masaharu Noda
Protein tyrosine phosphatase receptor type Z (PTPRZ) maintains oligodendrocyte precursor cells (OPCs) in an undifferentiated state. The inhibition of PTPase by its ligand pleiotrophin (PTN) promotes OPC differentiation; however, the substrate molecules of PTPRZ involved in the differentiation have not yet been elucidated in detail. We herein demonstrated that the tyrosine phosphorylation of AFAP1L2, paxillin, ERBB4, GIT1, p190RhoGAP, and NYAP2 was enhanced in OPC-like OL1 cells by a treatment with PTN. AFAP1L2, an adaptor protein involved in the PI3K-AKT pathway, exhibited the strongest response to PTN...
January 22, 2019: Glia
Yukishige Kimura, Atsushi Kuno, Masaya Tanno, Tatsuya Sato, Kouhei Ohno, Satoru Shibata, Kei Nakata, Hirohito Sugawara, Koki Abe, Yusuke Igaki, Toshiyuki Yano, Takayuki Miki, Tetsuji Miura
INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a risk factor of acute kidney injury (AKI) after myocardial infarction (MI), a form of cardiorenal syndrome (CRS). Recent clinical trials have shown that an SGLT2 inhibitor improved both cardiac and renal outcomes in patients with T2DM, but effects of an SGLT2 inhibitor on CRS remain unclear. MATERIALS AND METHODS: T2DM (OLETF) and control (LETO) rats were treated with canagliflozin, an SGLT2 inhibitor, for 2 weeks...
January 21, 2019: Journal of Diabetes Investigation
Madhavi J Rane, Yuguang Zhao, Lu Cai
Dysregulated Krϋppel-like factor (KLF) gene expression appears in many disease-associated pathologies. In this review, we discuss physiological functions of KLFs in the kidney with a focus on potential pharmacological modulation/therapeutic applications of these KLF proteins. KLF2 is critical to maintaining endothelial barrier integrity and preventing gap formations and in prevention of glomerular endothelial cell and podocyte damage in diabetic mice. KLF4 is renoprotective in the setting of AKI and is a critical regulator of proteinuria in mice and humans...
January 17, 2019: EBioMedicine
Yongping Chen, Li Luan, Chaoran Wang, Manyu Song, Yuan Zhao, Yujie Yao, Haotian Yang, Biao Ma, Honggang Fan
Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses multiple pharmacological actions. Herein, we explored the protective effect and potential molecular mechanism of DEX on lipopolysaccharide (LPS)-induced early acute kidney injury (AKI) from the perspective of antioxidant stress. We found that DEX (30 μg/kg, i.p.) ameliorated the renal dysfunction and histopathological damage (tubular necrosis, vacuolar degeneration, infiltration of inflammatory cells and cast formation) induced by LPS (10 mg/kg)...
January 16, 2019: Nitric Oxide: Biology and Chemistry
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