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Fibrosis kidney

Hongliang Zhang, Xiaojie Wei, Shunyu Lu, Xing Lin, Jianchun Huang, Lixiu Chen, Xiang Huang, Luhui Jiang, Yuchun Li, Luhui Qin, Jinbin Wei, Renbin Huang
BACKGROUND: Hyperglycemia stimulated epithelial-mesenchymal transition (EMT) plays a critical role in initiating and progressing renal fibrosis in diabetic kidney disease (DKD). It is crucial to explore novel renal protective drugs for the treatment of DKD. OBJECTIVE: The present study is to confirm our hypothesis and to accumulate the information for the application of DMDD (2-Dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione) as a novel therapeutic agent to potentially inhibit renal fibrogenesis and EMT in the DKD...
March 13, 2019: Biomedicine & Pharmacotherapy
Jung Beom Seo, Yeon Kyung Choi, Hye In Woo, Yun A Jung, Sungwoo Lee, Seunghyeong Lee, Mihyang Park, In Kyu Lee, Gwon Soo Jung, Keun Gyu Park
BACKGROUND: The hypoglycemic drugs dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although NOD-like receptor protein 3 (NLRP3) inflammasome activation is known to play an important role in the progression of renal fibrosis, the impact of DPP-4 inhibition on NLRP3-mediated inflammation while ameliorating renal fibrosis has not been fully elucidated. Here, we report that the renoprotective effect of gemigliptin is associated with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis...
March 5, 2019: Diabetes & Metabolism Journal
Po-Chun Chen, Wei-Yu Kao, Yuan-Lung Cheng, Yuan-Jen Wang, Ming-Chih Hou, Jaw-Ching Wu, Chien-Wei Su
BACKGROUND/PURPOSE: The impact of non-alcoholic fatty liver disease (NAFLD) on the prevalence of chronic kidney disease (CKD) is not fully elucidated. We aimed to assess the correlation between NAFLD and CKD in a large population study. METHODS: We included consecutive subjects who had received health check-up service at Taipei Veterans General Hospital from 2002 to 2009. NAFLD was diagnosed with abdominal ultrasound, and advanced liver fibrosis was determined with NAFLD fibrosis score (NAFLD-FS)...
March 12, 2019: Journal of the Formosan Medical Association
Juan Jin, Yifen Shi, Jianguang Gong, Li Zhao, Yiwen Li, Qiang He, He Huang
BACKGROUND: It is confirmed that adipose-derived stem cells (ADSCs) transplantation effectively relieves kidney fibrosis and type 2 diabetes disease in mice. Currently, exosome from urine-derived stem cells (USCs) can protect type 1 diabetes-mediated kidney injury and attenuate podocyte damage in diabetic nephropathy (DN). Exosome derived from USCs has evolved into the strategy for DN treatment, but the role of ADSCs-derived exosome (ADSCs-Exo) in DN remains unclear. The present study is aimed to investigate the therapeutic action and molecular mechanism of ADSCs-derived exosome on DN...
March 15, 2019: Stem Cell Research & Therapy
Xuan Peng, Yating Wang, Huiyan Li, Jinjin Fan, Jiani Shen, Xueqing Yu, Yi Zhou, Haiping Mao
G2/M-arrested proximal tubular epithelial cells (TECs) after renal injury are linked to increased cytokines production. ATG5-mediated autophagy in proximal TECs has recently been shown to protect against G2/M cell cycle arrest and renal fibrosis. However, the impacts of autophagy in regulating inflammatorily response mounted by injured TECs remains largely unknown. In the present study, we investigated whether ATG5 acts as an innate immune suppressor in proximal TECs during kidney injury. Using the unilateral ureteric obstruction model in proximal tubule-specific autophagy-deficient mice, we demonstrated that ablation of epithelial ATG5 genes markedly impaired autophagy, resulting in enhanced nuclear factor κB (NF-κB) activation, macrophage and lymphocyte infiltration, and proinflammatory cytokines production in obstructed kidneys, as compared with wild-type mice...
March 15, 2019: Cell Death & Disease
Yang Dong, Qunzi Zhang, Jiejun Wen, Teng Chen, Li He, Yiyun Wang, Jianyong Yin, Rui Wu, Rui Xue, Shiqi Li, Ying Fan, Niansong Wang
Ischemia reperfusion injury (IRI) is one of the most common causes of acute kidney injury (AKI). However, the pathogenesis and biomarkers predicting the progression of IRI-induced AKI to chronic kidney disease (CKD) remain unclear. A side-by-side comparison between different IRI animal models with variable ischemic duration and episodes was performed. The dynamic changes of KIM-1 and NGAL continuously from AKI to CKD phases were studied as well. Short-term duration of ischemia induced mild renal tubule-interstitial injury which was completely reversed at acute phase of kidney injury, while long-term duration of ischemia caused severe tubular damage, cell apoptosis and inflammatory infiltration at early disease stage, leading to permanent chronic kidney fibrosis at the late stage...
2019: Frontiers in Physiology
Monika Kubacka, Monika Zadrożna, Barbara Nowak, Magdalena Kotańska, Barbara Filipek, Anna Maria Waszkielewicz, Henryk Marona, Szczepan Mogilski
We investigated the therapeutic effect of MH-76 and MH-79, which are non-quinazoline α1-adrenoceptor antagonists with an additional ability to stimulate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/K + pathway, on deoxycorticosterone acetate (DOCA)-salt induced hypertension in rats. Prazosin was used as a reference compound, as quinazoline-based α1-adrenolytics may potentially exert unfavorable proapoptotic and necrotic effects. DOCA-salt hypertension was induced by DOCA (20 mg/kg s.c...
March 12, 2019: Hypertension Research: Official Journal of the Japanese Society of Hypertension
Cristina Grange, Stefania Tritta, Marta Tapparo, Massimo Cedrino, Ciro Tetta, Giovanni Camussi, Maria Felice Brizzi
Extracellular vesicles (EVs) that are derived from mesenchymal stromal cells (MSCs) have been shown to reprogram injured cells by activating regenerative processes. We herein investigate the potential therapeutic effect of EVs, shed by human bone marrow MSCs and by human liver stem-like cells (HLSCs), on the progression and reversion of fibrosis in a mouse model of diabetic nephropathy, as induced by streptozotocin. After the development of nephropathy, stem cell-derived EVs were administered weekly to diabetic mice for four weeks...
March 14, 2019: Scientific Reports
Turgay Saritas, Catherina A Cuevas, Mohammed Z Ferdaus, Christoph Kuppe, Rafael Kramann, Marcus J Moeller, Jürgen Floege, Jeffrey D Singer, James A McCormick
Cullin 3 (CUL3) is part of the ubiquitin proteasomal system and controls several cellular processes critical for normal organ function including the cell cycle, and Keap1/Nrf2 signaling. Kidney tubule-specific Cul3 disruption causes tubulointerstitial fibrosis, but little is known about the mechanisms. Therefore, we tested the hypothesis that dysregulation of the cell cycle and Keap1/Nrf2 pathway play a role in initiating the kidney injury upon Cul3 disruption. Cul3 deletion increased expression of cyclin E and p21, associated with uncontrolled proliferation, DNA damage, and apoptosis, all of which preceded proximal tubule injury...
March 14, 2019: Scientific Reports
Shizuko Nagao, Masanori Kugita, Kanako Kumamoto, Aya Yoshimura, Kazuhiro Nishii, Tamio Yamaguchi
The anti-diuretic hormone arginine vasopressin is thought to be a detrimental factor in polycystic kidney disease (PKD). We previously reported that high water intake (HWI) reduced urine osmolality and urinary arginine vasopressin, improved renal function, and reduced the kidney/body weight ratio in PCK rats, an orthologous model of human PKD. In PKD patients, however, it is reported that HWI increases total kidney volume, urine volume, and urine sodium excretion, which could be a consequence of high salt intake...
2019: PloS One
Kirsten Madsen
The prevalence of chronic kidney diseases (CKD) is increasing worldwide with negative consequences to quality of life for the individual subjects and to national health economics.1 CKD patients are at risk of progressing to end-stage renal disease (ESRD) with the need of life-long dialysis or kidney transplantation. Renal tubulointerstitial fibrosis is the final common pathway of CKD promoting the consecutive loss of kidney function. This article is protected by copyright. All rights reserved.
March 14, 2019: Acta Physiologica
Jong Wook Choi, Chang Hwa Lee, Joon-Sung Park
Non-alcoholic fatty liver disease (NAFLD) is closely linked to insulin resistance and related adverse health outcomes. We investigated the non-invasive index of NAFLD that has the best performance in estimating the renal manifestations of metabolic disturbances. This nation-wide, cross-sectional study included 11,836 subjects, using various non-invasive assessments comprising routinely measured clinical and laboratory variables. The subjects were native Koreans aged 20 years or older and had no diabetes, history of liver or kidney disease...
2019: PeerJ
Janne Folke Bialik, Mei Ding, Pam Speight, Qinghong Dan, Maria Zena Miranda, Caterina Di Ciano-Oliveira, Michael M Kofler, Ori D Rotstein, Stine F Pedersen, Katalin Szászi, András Kapus
Epithelial injury is a key initiator of fibrosis but - in contrast to the previous paradigm - the epithelium in situ does not undergo wide-spread epithelial-mesenchymal/myofibroblast transition (EMT/EMyT). Instead, it assumes a Profibrotic Epithelial Phenotype (PEP) characterized by fibrogenic cytokine production. The transcriptional mechanisms underlying PEP are undefined. As we have shown that two RhoA/cytoskeleton-regulated transcriptional coactivators, Myocardin-related transcription factor (MRTF) and TAZ, are indispensable for EMyT, we asked if they might mediate PEP as well...
March 13, 2019: Scientific Reports
Megan Stevens, Christopher R Neal, Elena C Craciun, Maria Dronca, Steven J Harper, Sebastian Oltean
There is evidence to suggest that abnormal angiogenesis, inflammation, and fibrosis drive diabetic nephropathy (DN). However, there is no specific treatment to counteract these processes. We aimed to determine whether DIAVIT, a natural Vaccinium myrtillus (blueberry) and Hippophae Rhamnoides (sea buckthorn) extract, is protective in a model of type II DN. Diabetic db/db mice were administered DIAVIT in their drinking water for 14 weeks. We assessed the functional, structural, and ultra-structural phenotype of three experimental groups (lean+vehicle, db/db+vehicle, db/db+DIAVIT)...
2019: PloS One
Yucheng Wu, Junlin Zhang, Jiali Wang, Yiting Wang, Qianqian Han, Hanyu Li, Tingli Wang, Fang Liu
AIM: To explore the relationship between serum bilirubin concentration with clinicopathological features and renal outcome in biopsy-diagnosed diabetic nephropathy (DN) in patients with type 2 diabetes mellitus (T2DM). METHODS: In this retrospective study, 118 patients with DN were enrolled. Participants were divided into two groups according to their median baseline serum bilirubin concentration: Group 1 (serum bilirubin ≤ 7.5μmol/L); Group 2 (serum bilirubin >7...
March 13, 2019: Endocrine Practice
Bo Zhang, Peihua Liu, Yan Zhou, Zhi Chen, Yao He, Miao Mo, Guoyu Dai, Weiping Xia, Yongchao Du, Yuhang Liu, Xiang Chen
AIMS: Renal fibrosis is the most common final stage of progressive renal disease, characterized by fibroblast proliferation, fibroblast-to-myofibroblast differentiation and excessive accumulation of extracellular matrix. Dihydroartemisinin (DHA) exerts antitumor, antibacterial, and antifibrotic effects. The aim of this study was to determine whether DHA has beneficial effects on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice and to examine explore the underlying possible mechanisms...
March 9, 2019: Life Sciences
Pietro E Cippà, Jing Liu, Bo Sun, Sanjeev Kumar, Maarten Naesens, Andrew P McMahon
The mechanisms initiating late immune responses to an allograft are poorly understood. Here we show, via transcriptome analysis of serial protocol biopsies from kidney transplants, that the initial responses to kidney injury correlate with a late B lymphocyte signature relating to renal dysfunction and fibrosis. With a potential link between dysfunctional repair and immunoreactivity, we investigate the immunological consequences of dysfunctional repair examining chronic disease in mouse kidneys 18 months after a bilateral ischemia/reperfusion injury event...
March 11, 2019: Nature Communications
Gabriela M Marchetti, Timothy J Burwell, Norman C Peterson, Jennifer A Cann, Richard N Hanna, Qing Li, Emily L Ongstad, Jonathan T Boyd, Maureen A Kennedy, Weiguang Zhao, Keith W Rickert, Joseph S Grimsby, William F Dall'Acqua, Herren Wu, Ping Tsui, M Jack Borrok, Ruchi Gupta
Systemic administration of bio-therapeutics can result in only a fraction of drug reaching targeted tissues, with the majority of drug being distributed to tissues irrelevant to the drug's site of action. Targeted delivery to specific organs may allow for greater accumulation, better efficacy, and improved safety. We investigated how targeting plasmalemma vesicle-associated protein (PV1), a protein found in the endothelial caveolae of lungs and kidneys, can promote accumulation in these organs. Using ex vivo fluorescence imaging, we show that intravenously administered αPV1 antibodies localize to mouse lungs and kidneys...
2019: Communications Biology
Yong Liu, Xianjin Bi, Jiachuan Xiong, Wenhao Han, Tangli Xiao, Xinli Xu, Ke Yang, Chi Liu, Wei Jiang, Ting He, Yanlin Yu, Yan Li, Jingbo Zhang, Bo Zhang, Jinghong Zhao
Renal fibrosis is the main pathological characteristic of chronic kidney disease (CKD), whereas the underlying mechanisms of renal fibrosis are not clear yet. Herein, we found an increased expression of microRNA-34a (miR-34a) in renal tubular epithelial cells of patients with renal fibrosis and mice undergoing unilateral ureteral obstruction (UUO). In miR-34a-/- mice, miR-34a deficiency attenuated the progression of renal fibrosis following UUO surgery. The miR-34a overexpression promoted epithelial-to-mesenchymal transition (EMT) in cultured human renal tubular epithelial HK-2 cells, which was accompanied by sharp downregulation of Klotho, an endogenous inhibitor of renal fibrosis...
February 15, 2019: Molecular Therapy: the Journal of the American Society of Gene Therapy
Giuseppe Mamone, Vincenzo Carollo, Kelvin Cortis, Sarah Aquilina, Rosa Liotta, Roberto Miraglia
Fibropolycystic liver diseases, also known as ductal plate malformations, are a group of associated congenital disorders resulting from abnormal development of the biliary ductal system. These disorders include congenital hepatic fibrosis, biliary hamartomas, polycystic liver disease, choledochal cysts and Caroli disease. Recently, it has been thought to include biliary atresia in this group of diseases, because ductal plate malformations could be implicated in the pathogenesis of this disease. Concomitant associated renal anomalies can also be present, such as autosomal recessive polycystic kidney disease (ARPKD), medullary sponge kidney and nephronophthisis...
March 9, 2019: Abdominal Radiology
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