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Smad7 AND Fibrosis

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https://www.readbyqxmd.com/read/28499242/potential-ameliorative-effects-of-grape-seed-derived-polyphenols-against-cadmium-induced-prostatic-deficits
#1
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...
May 9, 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
#2
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)...
April 24, 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
#3
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
#4
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
https://www.readbyqxmd.com/read/28352366/prolyl-oligopeptidase-attenuates-hepatic-stellate-cell-activation-through-induction-of-smad7-and-ppar-%C3%AE
#5
Da Zhou, Jing Wang, Ling-Nan He, Bing-Hang Li, Yong-Nian Ding, Yuan-Wen Chen, Jian-Gao Fan
Prolyl oligopeptidase (POP) is a serine endopeptidase widely distributed in vivo with high activity in the liver. However, its biological functions in the liver have remained largely elusive. A previous study by our group has shown that POP produced N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) and thereby exerted an anti-fibrogenic effect on hepatic stellate cells (HSCs) in vitro. It was therefore hypothesized that POP may affect the activation state of HSCs and has an important role in liver fibrosis. The HSC-T6 immortalized rat liver stellate cell line was treated with the POP inhibitor S17092 or transfected with recombinant lentivirus to overexpress POP...
February 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28339457/targeted-aav5-smad7-gene-therapy-inhibits-corneal-scarring-in-vivo
#6
Suneel Gupta, Jason T Rodier, Ajay Sharma, Elizabeth A Giuliano, Prashant R Sinha, Nathan P Hesemann, Arkasubhra Ghosh, Rajiv R Mohan
Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring...
2017: PloS One
https://www.readbyqxmd.com/read/28284148/effect-enhancing-and-toxicity-reducing-activity-of-usnic-acid-in-ascitic-tumor-bearing-mice-treated-with-bleomycin
#7
Zu-Qing Su, Yu-Hong Liu, Hui-Zhen Guo, Chao-Yue Sun, Jian-Hui Xie, Yu-Cui Li, Jian-Nan Chen, Xiao-Ping Lai, Zi-Ren Su, Hai-Ming Chen
Usnic acid (UA) can be found in certain lichen species. Growing evidence suggests that UA possesses antitumoral, antioxidative and anti-inflammatory activities. Bleomycin (BLM) is widely used in the treatment of malignant ascites, however, it unexpectedly causes pulmonary fibrosis (PF). Researches show that excessive inflammatory response and oxidative stress in lung tissue is conspicuous causes of BLM-induced PF. Here we investigated mechanism underlying the effect-enhancing and toxicity-reducing activity of UA on H22-bearing mice treated with BLM...
March 8, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28208683/plasma-gelsolin-induced-glomerular-fibrosis-via-the-tgf-%C3%AE-1-smads-signal-transduction-pathway-in-iga-nephropathy
#8
Lei Zhang, Changsong Han, Fei Ye, Yan He, Yinji Jin, Tianzhen Wang, Yiqi Wu, Yang Jiang, Fengmin Zhang, Xiaoming Jin
Glomerular fibrosis has been shown to be closely related to the progression and prognosis of IgA nephropathy (IgAN). However, mechanism underlying IgAN glomerular fibrosis remains unclear. Recently, our study showed that plasma gelsolin (pGSN) was decreased in the serum of an IgAN mouse model and that pGSN deposition was found in the glomeruli. Another cytokine, TGF-β1, which is closely related to glomerular fibrosis, was also found to be highly expressed in the glomeruli. In the present study, we report that pGSN induces glomerular fibrosis through the TGF-β1/Smads signal transduction pathway...
February 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28108300/tieg1-represses-smad7-mediated-activation-of-tgf-%C3%AE-1-smad-signaling-in%C3%A2-keloid-pathogenesis
#9
Zhi-Cheng Hu, Fen Shi, Peng Liu, Jian Zhang, Dong Guo, Xiao-Ling Cao, Chu-Fen Chen, Shan-Qiang Qu, Jia-Yuan Zhu, Bing Tang
Transforming growth factor-β (TGF-β)/Smad signaling plays a key role in excessive fibrosis and keloid formations. Smad7 is a negative feedback regulator that prevents activation of TGF-β/Smad signaling. However, the regulatory mechanism for Smad7 in the keloid pathogenic process remains elusive. Here, we show that expression of TIEG1 is markedly higher in keloid fibroblasts, whereas protein, mRNA, and promoter activity levels of Smad7 are decreased. When TIEG1 was knocked down with small interfering RNA, both the promoter activity and protein expression of Smad7 were increased, whereas collagen production and the proliferation, migration, and invasion of keloid fibroblasts were decreased...
May 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27991776/capsaicin-inhibits-dimethylnitrosamine-induced-hepatic-fibrosis-by-inhibiting-the-tgf-%C3%AE-1-smad-pathway-via-peroxisome-proliferator-activated-receptor-gamma-activation
#10
Jae Ho Choi, Sun Woo Jin, Chul Yung Choi, Hyung Gyun Kim, Gi Ho Lee, Yong An Kim, Young Chul Chung, Hye Gwang Jeong
Capsaicin (CPS) exerts many pharmacological effects, but any possible influence on liver fibrosis remains unclear. Therefore, we evaluated the inhibitory effects of CPS on dimethylnitrosamine (DMN) and TGF-β1-induced liver fibrosis in rats and hepatic stellate cells (HSCs). CPS inhibited DMN-induced hepatotoxicity, NF-κB activation, and collagen accumulation. CPS also suppressed the DMN-induced increases in α-SMA, collagen type I, MMP-2, and TNF-α. In addition, CPS inhibited DMN-induced TGF-β1 expression (from 2...
January 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27990439/effect-of-exogenous-fetuin-a-on-tgf-%C3%AE-smad-signaling-in-hepatic-stellate-cells
#11
Yulai Zhou, Shuang Yang, Pan Zhang
Objective. To explore the effects of low concentration of exogenous fetuin-A intervention on TGF-β1 induced LX2 cells through detection of the expression of mRNA and protein of Smad2, Smad3, and Smad7. Methods. MTT assay was used to detect the LX2 cells proliferation and the regression equation calculating software was applied to determine IC50 of fetuin-A. RT-PCR was used to determine the relative content of Smad2, Smad3, and Smad7 mRNA in LX2 cells. Western blot was used to detect the LX2 cells relative content of Smad2, Smad3, Smad7 protein expression, respectively...
2016: BioMed Research International
https://www.readbyqxmd.com/read/27876602/genistein-attenuates-d-galn-induced-liver-fibrosis-chronic-liver-damage-in-rats-by-blocking-the-tgf-%C3%AE-smad-signaling-pathways
#12
Ajaz Ahmad Ganai, Mohammad Husain
BACKGROUND AND AIM: Genistein is a major isoflavonoid abundantly found in soy. Earlier genistein has been reported to possess protective effect against a multitude of disorders including cancer. Previously we demonstrated the protective effects of Genistein in d-Galactosamine (D-GalN) induced fulminant hepatic failure (FHF) in rats. In present study, we evaluated the hepatoprotective activity of Genistein in rat model of chronic liver damage and liver fibrosis. METHODS: Liver fibrosis was induced by intraperitoneal injection of D-GalN (250 mg/kg BW) twice a week for 12 weeks...
January 5, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27872076/antischistosomiasis-liver-fibrosis-effects-of-chlorogenic-acid-through-il-13-mir-21-smad7-signaling-interactions-in-vivo-and-in-vitro
#13
Yao Wang, Fan Yang, Jun Xue, Xuan Zhou, Lei Luo, Qian Ma, Yun-Fei Chen, Juan Zhang, Shu-Ling Zhang, Lei Zhao
This study investigated the antischistosomiasis liver fibrosis effects of chlorogenic acid (CGA) on interleukin 13 (IL-13)/microRNA-21 (miR-21)/Smad7 signaling interactions in the hepatic stellate LX2 cell line and schistosome-infected mice. The transfection was based on the ability of the GV273-miR-21-enhanced green fluorescent protein (EGFP) and GV369-miR-21-EGFP lentiviral system to up- or downregulate the miR-21 gene in LX2 cells. The mRNA expression of miR-21, Smad7, and connective tissue growth factor (CTGF) and the protein expression of Smad7, CTGF, Smad1, phosphor-Smad1 (p-Smad1), Smad2, p-Smad2, Smad2/3, p-Smad2/3, transforming growth factor β (TGF-β) receptor I, and α-smooth muscle actin (α-SMA) was assayed...
February 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27870967/osthole-inhibits-the-expressions-of-collagen-i-and-iii-through-smad-signaling-pathway-after-treatment-with-tgf-%C3%AE-1-in-mouse-cardiac-fibroblasts
#14
Jin-Cheng Liu, Feng Wang, Mei-Lin Xie, Zong-Qi Cheng, Qiong Qin, Lin Chen, Rong Chen
BACKGROUND: Osthole, a natural coumarin and bioactive compound isolated from the fruit of Cnidium monnieri (L.) Cusson, was reported to prevent isoprenaline-induced myocardial fibrosis in mice by inhibiting the transforming growth factor-β1 (TGF-β1) expression, but the underlying mechanism is still unclear. The aim of this study is to illuminate whether the mechanism of osthole inhibiting collagen I and III expressions is associated with Smad signaling pathway in mouse cardiac fibroblasts (CFs) treated with TGF-β1...
February 1, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27855406/scoparone-protects-against-pancreatic-fibrosis-via-tgf-%C3%AE-smad-signaling-in-rats
#15
Min Xu, Jing Cai, Hong Wei, Meng Zhou, Ping Xu, Hongmei Huang, Wanxin Peng, Fengyi Du, Aihua Gong, Youli Zhang
BACKGROUND/AIMS: This study was to investigate the influence of scoparone on pancreatic fibrosis in vitro and in vivo. METHODS: Pancreatic stellate cells (PSCs) were isolated from pancreas tissue blocks, and cultured for 3-5 generations for the experiment. PSCs were treated with scoparone in different doses as experimental groups, salvianolic acid B as a positive control and PBS as a blank group. We measured the effects of scoparone on cellular proliferation, oxidative stress, epithelial-mesenchymal transition (EMT), and pancreatic fibrosis...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27747000/suberoylanilide-hydroxamic-acid-attenuates-paraquat-induced-pulmonary-fibrosis-by-preventing-smad7-from-deacetylation-in-rats
#16
Shan-Shan Rao, Xiang-Yan Zhang, Ming-Jun Shi, Ying Xiao, Ying-Ying Zhang, Yuan-Yuan Wang, Chang-Zhi Zhang, Song-Jun Shao, Xin-Mei Liu, Bing Guo
BACKGROUND: Recent evidence suggests that a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), has anti-fibrotic effect. However, the exact mechanism of its anti-fibrotic potential remains is unclear. In this study, we investigated the molecular mechanism of SAHA in attenuating pulmonary fibrosis by regulating stability of Smad7 in paraquat (PQ)-induced lung fibrosis animal model and cultured pulmonary fibroblasts. METHODS: Rats with paraquat-induced lung fibrosis were fed with a SAHA solution (15 mg/kg) by gastric gavage...
September 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/27722012/rhus-verniciflua-stokes-attenuates-cholestatic-liver-cirrhosis-induced-interstitial-fibrosis-via-smad3-down-regulation-and-smad7-up-regulation
#17
Mi Na Gil, Du Ri Choi, Kwang Sik Yu, Ji Heun Jeong, Dong-Ho Bak, Do-Kyung Kim, Nam-Seob Lee, Je-Hun Lee, Young-Gil Jeong, Chun Soo Na, Dae Seung Na, Ki-Hyun Ryu, Seung Yun Han
Cholestatic liver cirrhosis (CLC) eventually proceeds to end-stage liver failure by mediating overwhelming deposition of collagen, which is produced by activated interstitial myofibroblasts. Although the beneficial effects of Rhus verniciflua Stokes (RVS) on various diseases are well-known, its therapeutic effect and possible underlying mechanism on interstitial fibrosis associated with CLC are not elucidated. This study was designed to assess the protective effects of RVS and its possible underlying mechanisms in rat models of CLC established by bile duct ligation (BDL)...
September 2016: Anatomy & Cell Biology
https://www.readbyqxmd.com/read/27703175/paracrine-effects-of-adipose-derived-stem-cells-on-matrix-stiffness-induced-cardiac-myofibroblast-differentiation-via-angiotensin-ii-type-1-receptor-and-smad7
#18
Kar Wey Yong, Yuhui Li, Fusheng Liu, Bin Gao, Tian Jian Lu, Wan Abu Bakar Wan Abas, Wan Kamarul Zaman Wan Safwani, Belinda Pingguan-Murphy, Yufei Ma, Feng Xu, Guoyou Huang
Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary to develop an in vitro cardiac fibrosis model that incorporates pore size and native tissue-mimicking matrix stiffness, which may regulate cardiac myofibroblast differentiation. In the present study, collagen coated polyacrylamide hydrogel substrates were fabricated, in which the pore size was adjusted without altering the matrix stiffness...
October 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27687492/single-cell-analysis-reveals-igf-1-potentiation-of-inhibition-of-the-tgf-%C3%AE-smad-pathway-of-fibrosis-in-human-keratocytes-in-vitro
#19
Tomislav Sarenac, Martin Trapecar, Lidija Gradisnik, Marjan Slak Rupnik, Dusica Pahor
Corneal wound healing is often affected by TGF-β-mediated fibrosis and scar formation. Guided fibrosis with IGF-1 and antifibrotic substances might maintain corneal transparency. Primary human corneal keratocytes under serum-free conditions were used as a model of corneal stromal wounding, with markers of corneal fibrosis and opacity studied under TGF-β2 stimulation. Single-cell imaging flow cytometry was used to determine nuclearization of Smad3, and intracellular fluorescence intensity of Smad7 and the corneal crystallin aldehyde dehydrogenase 3A1...
September 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27633729/anti-hepatic-fibrosis-effects-of-a-novel-turtle-shell-decoction-by-inhibiting-hepatic-stellate-cell-proliferation-and-blocking-tgf-%C3%AE-1-smad-signaling-pathway-in-rats
#20
Ganping Bai, Guohe Yan, Guojian Wang, Ping Wan, Ronghua Zhang
Hepatic fibrosis (HF), a wound-healing response to a variety of chronic stimuli, is characterized by the excessive synthesis of extracellular matrix (ECM) proteins by hepatic stellate cells (HSC) and eventually the development of hepatic cirrhosis. Turtle shell pill (TSP) is a common traditional Chinese medicine used for preventing and treating HF and early hepatic cirrhosis, but its side-effects and the shortage of ingredients limit its clinical application. In addition, its mechanism of action is not clear...
November 2016: Oncology Reports
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