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Smad7 AND Fibrosis

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https://www.readbyqxmd.com/read/29138820/matrine-suppresses-cardiac-fibrosis-by-inhibiting-the-tgf%C3%A2-%C3%AE-smad-pathway-in-experimental-diabetic-cardiomyopathy
#1
Yong Zhang, Lei Cui, Gongchang Guan, Junkui Wang, Chuan Qiu, Tielin Yang, Yan Guo, Zhongwei Liu
Cardiac fibrosis is one of the pathological characteristics of diabetic cardiomyopathy (DbCM). Matrine treatment has proven to be effective in cases of organ fibrosis and cardiovascular diseases. In the present study, the anti-fibrosis-associated cardioprotective effects of matrine on DbCM were investigated. Rats with experimental DbCM were administered matrine orally. Cardiac functions were evaluated using invasive hemodynamic examinations. Cardiac compliance was assessed in isolated hearts. Using Sirius Red and fluorescence staining, the collagen in diabetic hearts was visualized...
November 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29115512/protective-effect-of-diltiazem-on-myocardial-ischemic-rats-induced-by-isoproterenol
#2
Yuejiao Wei, Tianyu Meng, Chaofeng Sun
The aim of the present study was to analyze the effect of diltiazem on myocardial fibrosis and remodeling of connexin43 (Cx43) in myocardial ischemic rats and mechanisms underlying these processes. A total of 36 Sprague‑Dawley rats were randomly allocated into three groups (control, isoproterenol and isoproterenol with diltiazem). The myocardial ischemic model was established by 5 mg/kg/day isoproterenol administration for 7 days, and the diltiazem group received 25 mg/kg/day diltiazem for 4 weeks. Following the treatment, paraffin sections were prepared to observe microstructural changes and to evaluate the concentration of Ca2+ in myocardium...
October 26, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29104654/mast-cell-chymase-promotes-hypertrophic-scar-fibroblast-proliferation-and-collagen-synthesis-by-activating-tgf-%C3%AE-1-smads-signaling-pathway
#3
Hongming Chen, Yanwen Xu, Guanbin Yang, Qianqian Zhang, Xun Huang, Liming Yu, Xianglin Dong
The present study assessed the existence of mast cell chymase in hypertrophic scars and determined whether chymase promotes fibrosis via the transforming growth factor (TGF)-β1/Smads signaling pathway. Five patients with hypertrophic scars and another five patients subjected to repair and reconstruction of other tissue defects were included in the present study. To detect the existence of mast cells and mast cell chymase in hypertrophic scars, immunohistochemistry was employed. To test the effect of chymase on TGF-β1, angiotensin, and type I and III collagen mRNA expression in isolated hypertrophic scar fibroblasts in vitro, reverse-transcription quantitative PCR was performed...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29102563/tgf-%C3%AE-mediates-renal-fibrosis-via-the-smad3-erbb4-ir-long-noncoding-rna-axis
#4
Min Feng, Patrick Ming-Kuen Tang, Xiao-Ru Huang, Si-Fan Sun, Yong-Ke You, Jun Xiao, Lin-Li Lv, An-Ping Xu, Hui-Yao Lan
Transforming growth factor β (TGF-β)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-β/Smad3-mediated renal fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-β1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-β1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-β/Smad3 signaling...
October 5, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29033951/sphingosine-1-phosphate-receptor-5-modulates-early-stage-processes-during-fibrogenesis-in-a-mouse-model-of-systemic-sclerosis-a-pilot-study
#5
Katrin G Schmidt, Martina Herrero San Juan, Sandra Trautmann, Lucija Berninger, Anja Schwiebs, Florian M Ottenlinger, Dominique Thomas, Frank Zaucke, Josef M Pfeilschifter, Heinfried H Radeke
Systemic sclerosis (SSc) is a rare multi-organ autoimmune disease characterized by progressive skin fibrosis. Inflammation, type 2 immunity, and fibrogenic processes are involved in disease development and may be affected by sphingolipids. However, details about early-stage pathophysiological mechanisms and implicated mediators remain elusive. The sphingolipid sphingosine-1-phosphate (S1P) is elevated in the sera of SSc patients, and its receptor S1P5 is expressed in skin tissue. Nevertheless, almost nothing is known about the dermatological contribution of S1P5 to inflammatory and pro-fibrotic processes leading to the pathological changes seen in SSc...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28983617/creb1-and-smad3-mediate-tgf%C3%A2-%C3%AE-3%C3%A2-induced-smad7-expression-in-rat-hepatic-stellate-cells
#6
Liang Deng, Lu Huang, Qiongya Guo, Xiaoyu Shi, Keshu Xu
Transforming growth factor (TGF)‑β3 has previously been reported to antagonize hepatic fibrosis in vivo and in vitro. The present study aimed to investigate the mechanism underlying the involvement of TGF‑β3 in hepatic fibrosis. Short hairpin (sh)RNA‑cAMP-responsive element binding protein (CREB) 1 and small interfering (si)RNA‑Smad3 were utilized to silence the expression of CREB1 and Smad3 in hepatic stellate cells (HSCs), whereas the vector pRSV‑CREB1 was used to induce CREB1 overexpression in HSCs...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28970517/human-in-vitro-model-reveals-the-effects-of-collagen-cross-linking-on-keratoconus-pathogenesis
#7
Rabab Sharif, Jesper Hjortdal, Henrik Sejersen, Garett Frank, Dimitrios Karamichos
Keratoconus (KC) is a corneal thinning disorder that leads to severe vision impairment As opposed to corneal transplantation; corneal collagen crosslinking (CXL) is a relatively non-invasive procedure that leads to an increase in corneal stiffness. In order to evaluate the effect of CXL on human corneal stromal cells in vitro, we developed a 3-D in vitro CXL model, using primary Human corneal fibroblasts (HCFs) from healthy patients and Human Keratoconus fibroblasts (HKCs) from KC patients. Cells were plated on transwell polycarbonate membranes and stimulated by a stable vitamin C...
October 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28962196/smad7-overexpressing-rat-bmscs-inhibit-the-fibrosis-of-hepatic-stellate-cells-by-regulating-the-tgf-%C3%AE-1-smad-signaling-pathway
#8
Shi-Pin Wu, Zhi Yang, Fu-Rong Li, Xiao-Di Liu, Hong-Tao Chen, Dong-Na Su
Mesenchymal stem cells (MSCs) are able to differentiate into hepatocytes, promote the regeneration of hepatic cells and inhibit the progression of hepatic fibrosis. Transforming growth factor (TGF)-β1 is one of the key factors in the development of liver fibrosis, which also promotes extracellular matrix (ECM) formation. Drosophila mothers against decapentaplegic 7 (Smad7) is an essential negative regulator in the TGF-β1/Smad signaling pathway. In the present study, bone mesenchymal stem cells (BMSCs) were isolated from rat bone marrow and transfected with lentiviral vectors carrying the Smad7 gene...
September 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28905939/curcumin-administration-suppresses-collagen-synthesis-in-the-hearts-of-rats-with-experimental-diabetes
#9
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
#10
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
#11
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
#12
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...
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
#13
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...
October 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
#14
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 using 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 with 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)...
November 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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