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Smad7 AND Fibrosis

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https://www.readbyqxmd.com/read/28905939/curcumin-administration-suppresses-collagen-synthesis-in-the-hearts-of-rats-with-experimental-diabetes
#1
Shuang Guo, Xiang-Wen Meng, Xiao-Song Yang, Xiu-Fen Liu, Chang-Han Ou-Yang, Chao Liu
Cardiac fibrosis is considered the initial change of diabetic cardiomyopathy (DCM). We have shown that curcumin alleviates collagen deposition in DCM, but the mechanism remains unknown. In this study we sought to investigate the effects of curcumin on cardiac fibrosis in vivo and in vitro and to elucidate the underlying mechanisms. Experimental diabetes was induced in rats by injection of low-dose streptozotocin (STZ) combined with high energy diet. The rats were orally treated with curcumin (300 mg·kg(-1)·d(-1)) for 16 weeks...
September 14, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28873458/anti-fibrotic-effects-of-valproic-acid-in-experimental-peritoneal-fibrosis
#2
Elerson C Costalonga, Luiza J de Freitas, Deise da S P Aragone, Filipe M O Silva, Irene L Noronha
BACKGROUND: Progressive fibrous thickening of the peritoneal membrane is a complication of long-term peritoneal dialysis (PD). TGF-β/Smad pathway activation, inflammation, and neoangiogenesis play important roles in peritoneal membrane (PM) changes induced by PD. Recently, histone deacetilase inhibitors (HDACi) have shown anti-fibrotic and anti-inflammatory effects in different experimental models. These drugs prevent deacetylation of histones causing a loosen chromatin, which in turn induce the expression of some anti-fibrotic genes...
2017: PloS One
https://www.readbyqxmd.com/read/28864168/liuweiwuling-tablets-attenuate-bdl-induced-hepatic-fibrosis-via-modulation-of-tgf-%C3%AE-smad-and-nf-%C3%AE%C2%BAb-signaling-pathways
#3
Huimin Liu, Fang Dong, Guangquan Li, Ming Niu, Congen Zhang, Yanzhong Han, Lanzhi He, Ping Yin, Bin Wang, Xiuxiu Sang, Ruishen Li, Jiabo Wang, Zhaofang Bai, Xiaohe Xiao
ETHNOPHARMACOLOGICAL RELEVANCE: Liuweiwuling (LWWL) tablets contain a six-herb Chinese formula and are commonly prescribed to facilitate nourishment of the liver and kidneys, clear away toxic materials and activate blood circulation. Administration of LWWL is well known for its protective effects on the liver and its capacity to confer long-term stability in patients exhibiting reduced transaminase levels. Clinical studies have reported that LWWL can also be used for the treatment of liver fibrosis with associated treatment regimens resulting in a concomitant reduction in transforming growth factor β1 (TGF-β1) levels in the serum of patients with hepatic fibrosis...
August 31, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28817807/mir-21-promotes-cardiac-fibrosis-after-myocardial-infarction-via-targeting-smad7
#4
Jinxia Yuan, Hongtao Chen, Dawei Ge, Yu Xu, Haihua Xu, Yang Yang, Ming Gu, Yuhe Zhou, Jingdong Zhu, Ting Ge, Qun Chen, Yue Gao, Yanqing Wang, Xiaowei Li, Yanfang Zhao
BACKGROUND/AIMS: Cardiac fibrosis after myocardial infarction (MI) has been identified as an important factor in the deterioration of heart function. Previous studies have demonstrated that miR-21 plays an important role in various pathophysiological processes in the heart. However, the role of miR-21 in fibrosis regulation after MI remains unclear. METHODS: To induce cardiac infarction, the left anterior descending coronary artery was permanently ligated of mice...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28808068/deletion-of-angiotensin-converting-enzyme-2-promotes-hypertensive-nephropathy-by-targeting-smad7-for-ubiquitin-degradation
#5
Zhen Liu, Xiao-Ru Huang, Hai-Yong Chen, Erik Fung, Jian Liu, Hui-Yao Lan
Angiotensin-converting enzyme-2 (ACE2) is downregulated in hypertensive nephropathy. The present study investigated the mechanisms whereby loss of ACE2 promoted angiotensin II-induced hypertensive nephropathy in ACE2 gene knockout mice. We found that compared with wild-type animals, mice lacking ACE2 developed much more severe hypertensive nephropathy in response to chronic angiotensin II infusion, including higher levels of blood pressure, urinary protein excretion, serum creatinine, and progressive renal fibrosis and inflammation...
August 14, 2017: Hypertension
https://www.readbyqxmd.com/read/28807595/sphingosine-kinase-2-deficiency-ameliorates-kidney-fibrosis-by-up-regulating-smad7-in-a-mouse-model-of-unilateral-ureteral-obstruction
#6
Stephanie Schwalm, Sandra Beyer, Helena Frey, Riad Haceni, Georgios Grammatikos, Dominique Thomas, Gerd Geisslinger, Liliana Schaefer, Andrea Huwiler, Josef Pfeilschifter
Kidney fibrosis is a hallmark of chronic kidney disease and leads to extracellular matrix accumulation, organ scarring, and loss of kidney function. In this study, we investigated the role of sphingosine kinase-2 (SPHK2) on the progression of tubular fibrosis by utilizing a mouse unilateral ureteral obstruction (UUO) model. We found that SPHK2 protein and activity are up-regulated in fibrotic renal tissue. Functionally, Sphk2 deficient (Sphk2(-/-)) mice showed an attenuated fibrotic response to UUO compared to wild-type mice as demonstrated by reduced collagen abundance and decreased expression of fibronectin-1, collagen I, α-smooth muscle actin, connective tissue growth factor (CTGF), and plasminogen activator inhibitor (PAI-1)...
August 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28706418/naringenin-prevents-experimental-liver-fibrosis-by-blocking-tgf%C3%AE-smad3-and-jnk-smad3-pathways
#7
Erika Hernández-Aquino, Natanael Zarco, Sael Casas-Grajales, Erika Ramos-Tovar, Rosa E Flores-Beltrán, Jonathan Arauz, Mineko Shibayama, Liliana Favari, Víctor Tsutsumi, José Segovia, Pablo Muriel
AIM: To study the molecular mechanisms involved in the hepatoprotective effects of naringenin (NAR) on carbon tetrachloride (CCl4)-induced liver fibrosis. METHODS: Thirty-two male Wistar rats (120-150 g) were randomly divided into four groups: (1) a control group (n = 8) that received 0.7% carboxy methyl-cellulose (NAR vehicle) 1 mL/daily p.o.; (2) a CCl4 group (n = 8) that received 400 mg of CCl4/kg body weight i.p. 3 times a week for 8 wk; (3) a CCl4 + NAR (n = 8) group that received 400 mg of CCl4/kg body weight i...
June 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28698735/cardioprotection-against-heart-failure-by-shenfu-injection-via-tgf-%C3%AE-smads-signaling-pathway
#8
Jingyu Ni, Yang Shi, Lan Li, Jingrui Chen, Lingyan Li, Min Li, Jinqiang Zhu, Yan Zhu, Guanwei Fan
OBJECTIVE: To explore the potential cardioprotective mechanism of Shenfu injection (SFI) against heart failure (HF) by attenuating myocardial fibrosis and cardiac remodeling. METHODS AND RESULTS: Four weeks after myocardial infarction (MI), adult male Sprague Dawley rats were randomized for 4-week treatment with Valsartan, SFI, or vehicle. Echocardiography and hemodynamics were applied to evaluate cardiac functions. Myocardia of coronary artery ligated (CAD) rats were observed to investigate changes in cardiac structure and function...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28685927/altering-equine-corneal-fibroblast-differentiation-through-smad-gene-transfer
#9
Todd L Marlo, Elizabeth A Giuliano, Ratnakar Tripathi, Ajay Sharma, Rajiv R Mohan
OBJECTIVE: To explore the impact of equine corneal fibroblast (ECF) to myofibroblast (ECM) differentiation by altering the expression of the Smad genes either individually or in combination. Specifically, we sought to examine the ECF differentiation after (a) silencing of Smad2, 3, and 4 profibrotic genes individually and (b) overexpression of antifibrotic Smad7 gene and in a combination with pro- and antifibrotic Smad genes. METHODS: Equine corneal fibroblast primary cultures were generated as previously described...
July 6, 2017: Veterinary Ophthalmology
https://www.readbyqxmd.com/read/28646304/ndrg2-knockdown-promotes-fibrosis-in-renal-tubular-epithelial-cells-through-tgf-%C3%AE-1-smad3-pathway
#10
Zhibo Jin, Chaohui Gu, Fengyan Tian, Zhankui Jia, Jinjian Yang
Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-β1-induced renal tubular epithelial cells (HK-2)...
June 23, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28638433/shenqiwan-ameliorates-renal-fibrosis-in-rats-by-inhibiting-tgf-%C3%AE-1-smads-signaling-pathway
#11
Hongshu Chen, Yiqing Xu, Yuanxiao Yang, Xiaojie Zhou, Shijie Dai, Changyu Li
Epithelial-mesenchymal transition (EMT) refers to the transition of epithelial cells into mesenchymal cells. Emerging evidence suggests that EMT is a key point in renal interstitial fibrosis (RIF). Traditional Chinese Medicine Shenqiwan (SQW) is widely used in clinical treatment of chronic kidney disease, but the underlying mechanism remains unclear. The purpose of this study is to investigate the effect of SQW on renal fibrosis and its association with TGF-β1/Smads signaling pathway. A rat model of adenine (150 mg/kg) was established and intragastrically treated with various concentrations of SQW at dose of 1...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28630605/xinfuli-granule-improves-post-myocardial-infarction-ventricular-remodeling-and-myocardial-fibrosis-in-rats-by-regulating-tgf-%C3%AE-smads-signaling-pathway
#12
Jie Ma, Zhi-Yuan Li, Xiao-Peng Liang, Cai-Xia Guo, Pei-Pei Lu, Li-Hong Ma
BACKGROUND: Recent clinical and experimental studies have confirmed the effects of Xinfuli Granule (XG), a compound Chinese medicine in the prevention and treatment of heart failure (HF). This study aimed to investigate the effects and the mechanisms of XG on ventricular reconstruction in rats with acute myocardial infarction (AMI). METHODS: Sprague-Dawley rats were subjected to left anterior descending branch ligation. The rats that survived 24 h were randomly assigned to five groups: medium-dose of XG group (MI+XGM), high-dose of XG group (MI+XGH), carvedilol group (MI+C), medium-dose of XG + carvedilol group (MI+C+XGM)...
May 2017: Journal of Geriatric Cardiology: JGC
https://www.readbyqxmd.com/read/28571007/eplerenone-prevents-atrial-fibrosis-via-the-tgf-%C3%AE-signaling-pathway
#13
Lili Du, Mu Qin, Yi Yi, Xiaoqing Chen, Weifeng Jiang, Li Zhou, Daoliang Zhang, Kai Xu, Yiqing Yang, Chao Li, Yan Liu, Xu Liu, Sheng-Zhong Duan
OBJECTIVES: Eplerenone (EPL), an antagonist of the mineralocorticoid receptor, is beneficial for atrial fibrillation and atrial fibrosis. However, the underlying mechanism remains less well known. We aimed to investigate the effect of EPL on atrial fibrosis using a mouse with selective atrial fibrosis and to explore the underlying mechanisms. METHODS: EPL-treated MHC-TGFcys33ser transgenic mice that have selective atrial fibrosis (Tx+EPL mice), as well as control mice, were used for in vivo studies including histological analyses, Western blotting, and qRT-PCR studies...
2017: Cardiology
https://www.readbyqxmd.com/read/28545667/arctigenin-suppresses-renal-interstitial-fibrosis-in-a-rat-model-of-obstructive-nephropathy
#14
Ao Li, Xiaoxun Zhang, Mao Shu, Mingjun Wu, Jun Wang, Jingyao Zhang, Rui Wang, Peng Li, Yitao Wang
BACKGROUND: Renal tubulointerstitial fibrosis (TIF) is commonly the final result of a variety of progressive injuries and leads to end-stage renal disease. There are few therapeutic agents currently available for retarding the development of renal TIF. PURPOSE: The aim of the present study is to evaluate the role of arctigenin (ATG), a lignan component derived from dried burdock (Arctium lappa L.) fruits, in protecting the kidney against injury by unilateral ureteral obstruction (UUO) in rats...
July 1, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28544244/branched-chain-amino-acids-supplementation-modulates-tgf-%C3%AE-1-smad-signaling-pathway-and-interleukins-in-ccl4-induced-liver-fibrosis
#15
Naglaa F Khedr, Eman G Khedr
The alterations and low levels of circulating branched chain amino acids (BCAAs), leucine, isoleucine, and valine, are associated with liver diseases. The study was designed to evaluate hepatoprotective effect of BCAAs on CCl4 -induced liver fibrosis and to investigate the molecular mechanisms underlying these effects in rats. In all, 30 male rats were divided into three groups. Control group (n = 10) and CCl4 group (n = 10), where rats were injected with CCl4 (1 mL/kg of 0.5 : 1 v/v injected i.p. twice weekly for 12 weeks)...
May 23, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28543554/smad3-expression-and-regulation-of-fibroplasia-in-vocal-fold-injury
#16
Nao Hiwatashi, Peter A Benedict, Gregory R Dion, Renjie Bing, Iv Kraja, Milan R Amin, Ryan C Branski
OBJECTIVE: Recent reports highlight the efficacy of small interfering RNA (siRNA) targeting SMAD3 to regulate transforming growth factor β (TGF-β)-mediated fibroplasia in vocal fold fibroblasts. The current study sought to investigate SMAD3 expression during wound healing in vivo and quantify the downstream transcriptional events associated with SMAD3 knockdown in vitro. STUDY DESIGN: In vivo and in vitro. METHODS: Unilateral vocal fold injury was created in a rabbit model...
September 2017: Laryngoscope
https://www.readbyqxmd.com/read/28499242/potential-ameliorative-effects-of-grape-seed-derived-polyphenols-against-cadmium-induced-prostatic-deficits
#17
Yongfang Lei, Qian Chen, Jinglou Chen, Dong Liu
Grape (Vitis vinifera) is consumed as fruit and wine for people. In this study, rat model of prostatic deficits was induced by orally receiving 60mg/L cadmium chlorine (CdCl2) through drinking water for 20 weeks. Grape seed-derived polyphenols extract (GSP) was orally given for 20 weeks. Finally, the prostatic levels of E-cadherin, fibronectin, and α-smooth muscle actin were measured by immunohistochemical and qPCR analysis. The oxidative stress was measured by detecting the levels of malondialdehyde, nitric oxide, reduced glutathione/oxidized glutathione and enzymatic antioxidant status...
July 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28439009/estrogen-receptor-%C3%AE-a-regulator-of-androgen-receptor-signaling-in-the-mouse-ventral-prostate
#18
Wan-Fu Wu, Laure Maneix, Jose Insunza, Ivan Nalvarte, Per Antonson, Juha Kere, Nancy Yiu-Lin Yu, Virpi Tohonen, Shintaro Katayama, Elisabet Einarsdottir, Kaarel Krjutskov, Yu-Bing Dai, Bo Huang, Wen Su, Margaret Warner, Jan-Åke Gustafsson
As estrogen receptor β(-/-) (ERβ(-/-)) mice age, the ventral prostate (VP) develops increased numbers of hyperplastic, fibroplastic lesions and inflammatory cells. To identify genes involved in these changes, we used RNA sequencing and immunohistochemistry to compare gene expression profiles in the VP of young (2-mo-old) and aging (18-mo-old) ERβ(-/-) mice and their WT littermates. We also treated young and old WT mice with an ERβ-selective agonist and evaluated protein expression. The most significant findings were that ERβ down-regulates androgen receptor (AR) signaling and up-regulates the tumor suppressor phosphatase and tensin homolog (PTEN)...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28414804/cyclosporine-a-alters-expression-of-renal-micrornas-new-insights-into-calcineurin-inhibitor-nephrotoxicity
#19
Jennifer L Gooch, Clayton King, Cynthia E Francis, Paul S Garcia, Yun Bai
Calcineurin inhibitors are powerful immunosuppressants that revolutionized organ transplantation. However, non-immune effects of the calcineurin inhibitor, such as cyclosporine A (CsA), have significantly hindered their use. Specifically, nephrotoxicity, which is associated with tubulointerstitial fibrosis, inflammation, and podocyte damage, affects up to half of all transplant patients. Calcineurin is involved in many aspects of kidney development and function; therefore, mechanisms of CsA-induced nephrotoxicity are complex and not yet fully understood...
2017: PloS One
https://www.readbyqxmd.com/read/28364097/-effect-of-lamivudine-and-silymarin-on-liver-fibrosis-relevant-factors-in-hbv-transgenic-mice-with-alcohol-drinking
#20
Juanjuan Huang, Shikun Liu, Zuojun Li, Libo Cao, Linqi Ouyang
To observe the role of lamividine and silymarin preventing and curing liver fibrosis-relevant factors induced by alcohol drinking in hepatitis B virus (HBV) transgenic mice (Tg mice).
 Methods: Forty HBV-Tg BALB/C mice with 1.3 copy were randomly divided into 4 groups: a control group, a model group, a lamivudine group and a silymarin group. Tg mice in control group were treated with normal saline via intragastric administration; Tg-mice in the model group were treated with 50% alcohol (5 mL/kg) once a day via intragastric administration; while Tg-mice in lamivudine group and silymarin group were treated with alcohol (5 mL/kg) plus laminvudine (100 mg/kg) and silymarin (200 mg/kg) once a day via intragastric administration respectively...
March 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
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