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Fibrosis renal

Junxia Wu, Xin Wan, Hao Zhang, Wenwen Li, Mengqing Ma, Binbin Pan, Xiubin Liang, Changchun Cao
BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms. METHODS: We established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration...
March 13, 2019: Biochemical and Biophysical Research Communications
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, Biomédecine & Pharmacothérapie
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
Robert Roskoski
Because mutations, overexpression, and dysregulation of protein kinases play essential roles in the pathogenesis of many illnesses, this enzyme family has become one of the most important drug targets in the past 20 years. The US FDA has approved 48 small molecule protein kinase inhibitors, nearly all of which are orally effective with the exceptions of netarsudil (which is given as an eye drop) and temsirolimus (which is given intravenously). Of the 48 approved drugs, the majority (25) target receptor protein-tyrosine kinases, ten target non-receptor protein-tyrosine kinases, and 13 target protein-serine/threonine protein kinases...
March 12, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Tianjiao Ma, Zongyu Zheng, Hua Guo, Xin Lian, Madhavi J Rane, Lu Cai, Ki Soo Kim, Kyoung Tae Kim, Zhiguo Zhang, Liqi Bi
Diabetic nephropathy (DN) is one of the most serious long-term complications of type 2 diabetes (T2D). 4-O-methylhonokiol (MH) is one of the biologically active ingredients extracted from the Magnolia stem bark. In this study, we aim to elucidate whether treatment with MH can ameliorate or slow-down progression of DN in a T2D murine model and, if so, whether the protective response of MH correlates with AMPK-associated anti-oxidant and anti-inflammatory effects. To induce T2D, mice were fed normal diet (ND) or high fat diet (HFD) for 3 months to induce insulin resistance, followed by an intraperitoneal injection of STZ to induce hyperglycemia...
March 12, 2019: Toxicology and Applied Pharmacology
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
Hongyan Li, Yuexia Xu, Qin Zhang, Hongfang Xu, Yan Xu, Kai Ling
Function and potential mechanism of microvesicles (MVs) containing microRNA34a in renal interstitial fibrosis were investigated. A rat model of renal interstitial fibrosis was established by unilateral ureteral ligation (UUO). Rat proximal tubular epithelial cell line (NRK-52E) was used to explore the effect of MVs containing microRNA-34a on tubular epithelial cells during fibrosis, which were secreted by tubulointerstitial fibroblasts. Regardless of the UUO renal interstitial fibrosis model, or the TGF-β1-treated renal tubular epithelial cells, microRNA-34a was increased in the MVs secreted by tubulointerstitial fibroblasts...
March 2019: Experimental and Therapeutic Medicine
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
A Reynolds, J A Keen, T Fordham, R A Morgan
BACKGROUND: Obesity is a common feature of equine metabolic syndrome (EMS). In other species obese adipose tissue shows pathological features such as adipocyte hypertrophy, fibrosis, inflammation and impaired insulin signalling all of which contribute to whole body insulin dysregulation. Such adipose tissue dysfunction has not been investigated in horses. OBJECTIVES: To determine if obese horses with EMS have adipose tissue dysfunction characterised by adipocyte hypertrophy, fibrosis, inflammation and altered insulin signalling...
March 13, 2019: Equine Veterinary Journal
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
Benoit Denhez, Marina Rousseau, David-Alexandre Dancosst, Farah Lizotte, Andréanne Guay, Mannix Auger-Messier, Anne Marie Côté, Pedro Geraldes
Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease. Hyperglycemia-induced podocyte dysfunction is a major contributor of renal function impairment in DN. Previous studies showed that activation of mitogen-activated protein kinase (MAPK) in diabetes promotes podocyte dysfunction and cell death. Dual specificity phosphatase (DUSP) are a family of phosphatases mainly responsible for MAPK inhibition. In this study, we demonstrated that diabetes and high glucose exposure decreased DUSP4 expression in cultured podocytes and glomeruli...
March 12, 2019: Diabetes
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
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