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https://www.readbyqxmd.com/read/29792841/decarboxylation-of-ang-1-7-to-ala-1-ang-1-7-leads-to-significant-changes-in-pharmacodynamics
#1
Anja Tetzner, Maura Naughton, Kinga Gebolys, Jenny Eichhorst, Esther Sala, Óscar Villacañas, Thomas Walther
The heptapeptide angiotensin (Ang)-(1-7) is part of the beneficial arm of the renin-angiotensin system. Ang-(1-7) has cardiovascular protective effects, stimulates regeneration, and opposes the often detrimental effects of Ang II. We recently identified the G protein-coupled receptors Mas and MrgD as receptors for the heptapeptide. Ala1 -Ang-(1-7) (Alamandine), a decarboxylated form of Ang-(1-7), has similar vasorelaxant effects, but has been described to only stimulate MrgD. Therefore, this study aimed to characterise the consequences of the lack of the carboxyl group in amino acid 1 on intracellular signalling and to identify the receptor fingerprint for Ala1 -Ang-(1-7)...
May 21, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29787774/silencing-of-paqr3-suppresses-extracellular-matrix-accumulation-in-high-glucose-stimulated-human-glomerular-mesangial-cells-via-pi3k-akt-signaling-pathway
#2
Huicong Li, Yunqian Wang, Baoping Chen, Jun Shi
Progestin and AdipoQ Receptor 3 (PAQR3), a member of the PAQR family, was involved in multiple biological processes, including tumorigenesis, cholesterol homeostasis, autophagy, obesity, insulin sensitivity and energy metabolism. However, the role of PAQR3 in diabetic nephropathy is still unclear. Therefore, in this study, we investigated the effects of PAQR3 on cell proliferation and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) cultured under high glucose (HG), and explored the underlying mechanism...
May 19, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29782856/sirt1-activation-prevents-anti-thy-1-1-mesangial-proliferative-glomerulonephritis-in-the-rat-through-the-nrf2-are-pathway
#3
Kaipeng Huang, Ruiming Li, Wentao Wei
Mesangial proliferative glomerulonephritis (MsPGN) is characterized by glomerular mesangial cells proliferation and extracellular matrix deposition in mesangial area, which develop into glomerulosclerosis. Both silent information regulator 2-related protein 1 (Sirt1) and nuclear factor erythroid 2-related factor 2/ anti-oxidant response element (Nrf2/ARE) pathway had remarkable renoprotective effects. However, whether Sirt1 and Nrf2/ARE pathway can regulate the pathological process of MsPGN remains unknown...
May 18, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29778909/n-acetylcysteine-protects-against-diabetic-nephropathy-through-control-of-oxidative-and-nitrosative-stress-by-recovery-of-nitric-oxide-in-rats
#4
Guilherme B Nogueira, Giovana R Punaro, Clemerson S Oliveira, Fabiane R Maciel, Thamires O Fernandes, Deyse Y Lima, Adelson M Rodrigues, Margaret G Mouro, Sergio R R Araujo, Elisa M S Higa
The diabetes mellitus (DM) induces several changes, with substantial increase of reactive oxygen species (ROS). The ROS cause damage to systemic and renal microvasculature, which could be one of the mechanisms involved in the development of diabetic nephropathy (DN). The ROS modulate other substances like the nitric oxide (NO), a vasodilator with important role in the renal function. N-acetylcysteine (NAC) is an antioxidant that acts replenishing intracellular cysteine levels, which is essential for glutathione formation...
May 17, 2018: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29774092/vorapaxar-treatment-reduces-mesangial-expansion-in-streptozotocin-induced-diabetic-nephropathy-in-mice
#5
Maaike Waasdorp, JanWillem Duitman, Sandrine Florquin, C Arnold Spek
Background: Twenty years after the onset of diabetes, up to 40% of patients develop diabetic nephropathy. Protease-activated receptor-1 (PAR-1) has recently been shown to aggravate the development of experimental diabetic nephropathy. PAR-1 deficient mice develop less albuminuria and glomerular lesions and PAR-1 stimulation induces proliferation and fibronectin production in mesangial cells in vitro . Vorapaxar is a clinically available PAR-1 inhibitor which is currently used for secondary prevention of ischemic events...
April 24, 2018: Oncotarget
https://www.readbyqxmd.com/read/29771991/progenitor-renin-lineage-cells-are-not-involved-in-the-regeneration-of-glomerular-endothelial-cells-during-experimental-renal-thrombotic-microangiopathy
#6
Leo Ruhnke, Jan Sradnick, Moath Al-Mekhlafi, Michael Gerlach, Florian Gembardt, Bernd Hohenstein, Vladimir T Todorov, Christian Hugo
Endothelial cells (EC) frequently undergo primary or secondary injury during kidney disease such as thrombotic microangiopathy or glomerulonephritis. Renin Lineage Cells (RLCs) serve as a progenitor cell niche after glomerular damage in the adult kidney. However, it is not clear whether RLCs also contribute to endothelial replenishment in the glomerulus following endothelial injury. Therefore, we investigated the role of RLCs as a potential progenitor niche for glomerular endothelial regeneration. We used an inducible tet-on triple-transgenic reporter strain mRen-rtTAm2/LC1/LacZ to pulse-label the renin-producing RLCs in adult mice...
2018: PloS One
https://www.readbyqxmd.com/read/29759420/lysyl-oxidase-like-2-contributes-to-renal-fibrosis-in-col4%C3%AE-3-alport-mice
#7
Dominic Cosgrove, Brianna Dufek, Daniel T Meehan, Duane Delimont, Michael Hartnett, Gina Samuelson, Michael Anne Gratton, Grady Phillips, Deidre A MacKenna, Gretchen Bain
Lysyl oxidase like-2 (LOXL2) is an amine oxidase with both intracellular and extracellular functions. Extracellularly, LOXL2 promotes collagen and elastin crosslinking, whereas intracellularly, LOXL2 has been reported to modify histone H3, stabilize SNAIL, and reduce cell polarity. Although LOXL2 promotes liver and lung fibrosis, little is known regarding its role in renal fibrosis. Here we determine whether LOXL2 influences kidney disease in COL4A3 (-/-) Alport mice. These mice were treated with a small molecule inhibitor selective for LOXL2 or with vehicle and assessed for glomerular sclerosis and fibrosis, albuminuria, blood urea nitrogen, lifespan, pro-fibrotic gene expression and ultrastructure of the glomerular basement membrane...
May 11, 2018: Kidney International
https://www.readbyqxmd.com/read/29728506/abrogation-of-lupus-nephritis-in-somatic-hypermutation-deficient-mrl-lpr-mice
#8
Fengqi Hao, Miaomiao Tian, Yunpeng Feng, Chao Quan, Yixi Chen, Shuai Chen, Min Wei
Systemic lupus erythematosus (SLE) is an autoimmune disease posing threats to multiple organs in the human body. As a typical manifestation of SLE, lupus nephritis is characterized by a series of pathological changes in glomerulus as well as accumulation of pathogenic autoreactive IgG with complement in the kidney that dramatically disrupts renal functions. Activation-induced deaminase (AID), which governs both somatic hypermutation (SHM) and class-switch recombination (CSR), has been shown to be essential for the regulation of SLE...
May 4, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29725042/reduced-autophagy-by-a-microrna-mediated-signaling-cascade-in-diabetes-induced-renal-glomerular-hypertrophy
#9
Supriya Deshpande, Maryam Abdollahi, Mei Wang, Linda Lanting, Mitsuo Kato, Rama Natarajan
Autophagy plays a key role in the pathogenesis of kidney diseases, however its role in diabetic nephropathy (DN), and particularly in kidney glomerular mesangial cells (MCs) is not very clear. Transforming Growth Factor- β1 (TGF-β), a key player in the pathogenesis of DN, regulates expression of various microRNAs (miRNAs), some of which are known to regulate the expression of autophagy genes. Here we demonstrate that miR-192, induced by TGF-β signaling, plays an important role in regulating autophagy in DN...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29722904/renal-complications-of-lipodystrophy-a-closer-look-at-the-natural-history-of-kidney-disease
#10
Baris Akinci, Sadiye Mehtat Unlu, Ali Celik, Ilgin Yildirim Simsir, Sait Sen, Banu Nur, Fatma Ela Keskin, Basak Ozgen Saydam, Nilufer Ozdemir Kutbay, Banu Sarer Yurekli, Bekir Ugur Ergur, Melda Sonmez, Tahir Atik, Atakan Arslan, Tevfik Demir, Canan Altay, Ulku Aybuke Tunc, Tugba Arkan, Ramazan Gen, Erdal Eren, Gulcin Akinci, Aslihan Arasli Yilmaz, Habip Bilen, Samim Ozen, Aygul Celtik, Senay Savas Erdeve, Semra Cetinkaya, Huseyin Onay, Sulen Sarioglu, Elif Arioglu Oral
OBJECTIVES: Lipodystrophy syndromes are a group of heterogeneous disorders characterized by adipose tissue loss. Proteinuria is a remarkable finding in previous reports. STUDY DESIGN: In this multi-center study, prospective follow-up data were collected from 103 subjects with non-HIV associated lipodystrophy registered in the Turkish Lipodystrophy Study Group database to study renal complications in treatment naïve patients with lipodystrophy. METHODS: Main outcome measures included ascertainment of chronic kidney disease (CKD) by studying the level of proteinuria and the estimated glomerular filtration rate (eGFR)...
May 3, 2018: Clinical Endocrinology
https://www.readbyqxmd.com/read/29710524/tangeretin-inhibits-high-glucose-induced-extracellular-matrix-accumulation-in-human-glomerular-mesangial-cells
#11
Fang Chen, Yali Ma, Zhiqiang Sun, Xiaoguang Zhu
Tangeretin (5, 6, 7, 8, 4'-pentamethoxyflavone), a natural compound extracted from citrus plants, has been shown to possess a variety of pharmacological activities, including anti-oxidant, anti-tumor, cytostatic and anti-diabetic properties. However, the role of tangeretin in diabetic nephropathy (DN) has not yet been investigated. This study was undertaken to elucidate the effects of tangeretin on high glucose (HG)-induced oxidative stress and extracellular matrix (ECM) accumulation in human glomerular mesangial cells (MCs) and explore the underlying mechanisms...
April 3, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29708439/acteoside-relieves-mesangial-cell-injury-by-regulating-th22-cell-chemotaxis-and-proliferation-in-iga-nephropathy
#12
Lu Gan, Xiaozhao Li, Mengyuan Zhu, Chen Chen, Huimin Luo, Qiaoling Zhou
The existing therapies of IgA nephropathy are unsatisfying. Acteoside, the main component of Rehmannia glutinosa with anti-inflammatory and anti-immune effects, can improve urinary protein excretion and immune disorder. Th22 cell is involved in IgA nephropathy progression. This study was determined to explore the effect of acteoside on mesangial injury underlying Th22 cell disorder in IgA nephropathy. Serum Th22 cells and urine total protein of patients with IgA nephropathy were measured before and after six months treatment of Rehmannia glutinosa acteoside or valsartan...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29705354/effect-of-tet2-on-the-pathogenesis-of-diabetic-nephropathy-through-activation-of-transforming-growth-factor-%C3%AE-1-expression-via-dna-demethylation
#13
Yang Liling, Zhang Qian, Wu Qiong, Wei Yi, Yu Jiawei, Mu Jiao, Zhang Jun, Zeng Wei, Feng Bing
AIMS: Transforming growth factor β1 (TGFβ1) plays a pivotal role in the pathogenesis of diabetic nephropathy (DN). However, the mechanism of its expression and activation induced by high glucose (HG) is still unclear. We mainly explored the role of ten-eleven translocation enzyme-2 (TET2) in regulating TGFβ1 expression in the process of DN. MAIN METHODS: Human mesangial cells (HMCs) and db/db mice were used to analyze the biological effects of hyperglycemia both in vivo and in vitro...
April 26, 2018: Life Sciences
https://www.readbyqxmd.com/read/29704532/mdm2-controls-nrf2-antioxidant-activity-in-prevention-of-diabetic-kidney-disease
#14
Weiying Guo, Dan Tian, Ye Jia, Wenlin Huang, Mengnan Jiang, Junnan Wang, Weixia Sun, Hao Wu
Oxidative stress and P53 contribute to the pathogenesis of diabetic kidney disease (DKD). Nuclear factor erythroid 2-related factor 2 (NRF2) is a master regulator of cellular antioxidant defense system, is negatively regulated by P53 and prevents DKD. Recent findings revealed an important role of mouse double minute 2 (MDM2) in protection against DKD. However, the mechanism remained unclear. We hypothesized that MDM2 enhances NRF2 antioxidant signaling in DKD given that MDM2 is a key negative regulator of P53...
April 25, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29701296/repression-of-microrna-382-inhibits-glomerular-mesangial-cell-proliferation-and-extracellular-matrix-accumulation-via-foxo1-in-mice-with-diabetic-nephropathy
#15
Shan Wang, Xin Wen, Xin-Rui Han, Yong-Jian Wang, Min Shen, Shao-Hua Fan, Juan Zhuang, Zi-Feng Zhang, Qun Shan, Meng-Qiu Li, Bin Hu, Chun-Hui Sun, Dong-Mei Wu, Jun Lu, Yuan-Lin Zheng
OBJECTIVES: Diabetic nephropathy (DN) is a nerve damaging disorder, characterized by glomerular mesangial cell expansion and accumulation of extracellular matrix (ECM) proteins. In this study, we aimed to investigate mesangial cell proliferation and ECM accumulation when promoting or suppressing endogenous miR-382 in glomerular mesangial cells of DN. MATERIALS AND METHODS: Model establishment consisted of DN induction by streptozotocin (STZ) in mice. The underlying regulatory mechanisms of miR-382 were analysed in concert with the treatment of miR-382 mimics, miR-382 inhibitors or siRNA against FoxO1 in cultured glomerular mesangial cells isolated from DN mice...
April 27, 2018: Cell Proliferation
https://www.readbyqxmd.com/read/29700282/lincrna-1700020i14rik-alleviates-cell-proliferation-and-fibrosis-in-diabetic-nephropathy-via-mir-34a-5p-sirt1-hif-1%C3%AE-signaling
#16
Ailing Li, Rui Peng, Yan Sun, Handeng Liu, Huimin Peng, Zheng Zhang
Long intergenic noncoding RNAs (lincRNAs) have been gradually identified to be functional in a variety of different mechanisms associating with development and epigenetic regulation of cellular homeostasis. However, the study of lincRNAs in diabetic nephropathy (DN) is still in its infancy. Here, we have found dysexpressed long noncoding RNAs (lncRNAs) in renal tissues of db/db DN mice compared with db/m mice by RNA sequencing. In this study, 5 lincRNAs were confirmed to express in a consistent trend among these DN-related lncRNAs both in vivo and in vitro...
April 27, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29681936/metformin-regulating-mir-34a-pathway-to-inhibit-egr1-in-rat-mesangial-cells-cultured-with-high-glucose
#17
Can Wu, Ningning Qin, Huiwen Ren, Min Yang, Shuang Liu, Qiuyue Wang
Background: Activating AMPK α negatively regulates Egr1 to inhibit inflammatory cytokines in high glucose. miR-34a inhibition increases phosphorylated AMPK α through mediating SIRT1 to suppress the development of fatty liver. Aim of the Study: To clarify the function of Egr1 on the inflammation and fibrosis in high glucose-cultured MCs, as well as to explore the effects of metformin on miR-34a pathway and Egr1 expression. Methods: We transfected MCs with miR-34a inhibitor...
2018: International Journal of Endocrinology
https://www.readbyqxmd.com/read/29675433/sweet-taste-receptors-mediated-ros-nlrp3-inflammasome-signaling-activation-implications-for-diabetic-nephropathy
#18
Luping Zhou, Wei Huang, Youhua Xu, Chenlin Gao, Ting Zhang, Man Guo, Yan Liu, Jingya Ding, Ludan Qin, Zihao Xu, Yang Long, Yong Xu
Previous studies demonstrated that ROS-NLRP3 inflammasome signaling activation was involved in the pathogenesis of diabetic nephropathy (DN). Recent research has shown that sweet taste receptors (STRs) are important sentinels of innate immunity. Whether high glucose primes ROS-NLRP3 inflammasome signaling via STRs is unclear. In this study, diabetic mouse model was induced by streptozotocin (STZ) in vivo; mouse glomerular mesangial cells (GMCs) and human proximal tubular cells were stimulated by high glucose (10, 20, and 30 mmol/L) in vitro; STR inhibitor lactisole was used as an intervention reagent to evaluate the role and mechanism of the STRs in the pathogenesis of DN...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29669307/long-non-coding-rna-neat1-plays-an-important-role-in-sepsis-induced-acute-kidney-injury-by-targeting-mir-204-and-modulating-the-nf-%C3%AE%C2%BAb-pathway
#19
REVIEW
Yi Chen, Jialing Qiu, Bin Chen, Youping Lin, Yulan Chen, Guojin Xie, Junming Qiu, Huasheng Tong, Dongxin Jiang
This study aimed to explore the role of long non-coding RNA NEAT1 in sepsis-induced acute kidney injury (AKI). The expression levels of NEAT1 in sepsis-induced AKI patients were detected. The rat mesangial cells (RMCs) were treated with lipopolysaccharide (LPS) to induce cell injury. Then, the effects of NEAT1 suppression on the cell viability, apoptosis, cytokines expression, and oxidative stress in the LPS-stimulated RMCs were tested. The regulatory miRNA of NEAT1, as well as the target genes of this miRNA, were investigated...
April 15, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29668344/phenotypic-plasticity-of-mesenchymal-stem-cells-is-crucial-for-mesangial-repair-in-a-model-of-immunoglobulin-light-chain-associated-mesangial-damage
#20
Guillermo A Herrera, Jiamin Teng, Chun Zeng, Hongzhi Xu, Man Liang, J Steven Alexander, Bing Liu, Chris Boyer, Elba A Turbat-Herrera
Mesangiopathies produced by glomerulopathic monoclonal immunoglobulin light chains (GLCs) acting on the glomerular mesangium produce two characteristic lesions: AL-amyloidosis (AL-Am) and light chain deposition disease (LCDD). In both cases, the pathology is centered in the mesangium, where initial and progressive damage occurs. In AL-Am the mesangial matrix is destroyed and replaced by amyloid fibrils and in LCDD, the mesangial matrix is increased and remodeled. The collagen IV rich matrix is replaced by tenascin...
April 18, 2018: Ultrastructural Pathology
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