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Smad7 AND Fibrosis

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
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
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
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
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...
September 9, 2016: Oncology Reports
Guangyao Zhou, Wei Lin, Peipei Fang, Xiuzhen Lin, Lu Zhuge, Zhiqiu Hu, Lingxiang Jin
The aim of the present study was to examine the expression variation of the mouse hepatic fibrosis tissue transforming growth factor (TGF)-βl/Smads signal transduction pathway and its correlation with progression of hepatic fibrosis. The promotion effect of microRNA (miR)-10a on hepatic fibrosis and its possible mechanism was also assessed. Forty healthy female 8-week-old C57BL6/J mice were randomly divided into the control group (intraperitoneal injection of 5 µl/g normal saline, twice per week for 8 weeks) and the hepatic fibrosis group (intraperitoneal injection of 5 µl/g 10% CCI4 olive oil, twice per week for 8 weeks), with 20 mice per group...
September 2016: Experimental and Therapeutic Medicine
Zuo-Wei Ning, Xiao-Ying Luo, Guo-Zhen Wang, Yang Li, Miao-Xia Pan, Ren-Qiang Yang, Xu-Guang Ling, Shan Huang, Xiao-Xin Ma, Si-Yi Jin, Dan Wang, Xu Li
Aims Angiotensin II (AngII), a vasoconstrictive peptide of the renin-angiotensin system, promotes hepatic fibrogenesis and induces microRNA-21 expression. Angiotensin-(1-7) [Ang-(1-7)], which counter-regulates Ang II, has been evidenced to protect against hepatic fibrosis. The NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, which is activated by reactive oxygen species, was identified as a novel mechanism of liver fibrosis. However, it remains unclear how microRNA-21 mediates AngII-induced NLRP3 inflammasome activation...
August 8, 2016: Antioxidants & Redox Signaling
Pei-Fang Hsieh, Shu-Fen Liu, Tsung-Jen Hung, Chien-Ya Hung, Guo-Zheng Liu, Lea-Yea Chuang, Mei-Fen Chen, Jue-Long Wang, Ming-Der Shi, Chen Hung Hsu, Yow-Ling Shiue, Yu-Lin Yang
Thymic stromal lymphopoietin (TSLP) has previously been linked to allergic inflammatory diseases, and tissue fibrosis and organ dysfunction may also arise from such inflammation. It remains unclear, however, whether TSLP plays any role in the occurrence of renal fibrosis, so this study investigated that possibility. An in vitro fibrosis model was established by treating normal rat kidney fibroblast (NRK-49F) cells with transforming growth factor-β1 (TGF-β1), after which the levels of various fibrogenic markers (e...
September 10, 2016: Experimental Cell Research
Cong Wang, Shen Gu, Honghui Cao, Zutong Li, Zou Xiang, Kebin Hu, Xiaodong Han
Myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSC) plays an important role in idiopathic pulmonary fibrosis. By comparing the expression profiles of miRNAs before and after myofibroblast differentiation of LR-MSC, we identified miR-877-3p as a fibrosis-related miRNA. We found that miR-877-3p sequestration inhibited the myofibroblast differentiation of LR-MSC and attenuates bleomycin-induced lung fibrosis by targeting Smad7. Smad7, as an inhibitory smad in the TGF-β1 signaling pathway, was decreased in the myofibroblast differentiation of LR-MSC and up-regulation of Smad7 could inhibit the differentiation process...
2016: Scientific Reports
Xing Li, Xiao-Qin Wu, Tao Xu, Xiao-Feng Li, Yang Yang, Wan-Xia Li, Cheng Huang, Xiao-Ming Meng, Jun Li
Liver fibrosis refers to a reversible wound healing process response to chronic liver injuries. Activation of hepatic stellate cells (HSCs) is closely correlated with the development of liver fibrosis. Histone deacetylases(HDACs) determine the acetylation levels of core histones to modulate expression of genes. To demonstrate the link between HDACs and liver fibrosis, CCl4-induced mouse liver fibrosis model and its spontaneous reversal model were established. Results of the current study demonstrated that deregulation of liver HDACs may involved in the development of liver fibrosis...
September 1, 2016: Toxicology and Applied Pharmacology
Xuan Li, Salvatore Nania, Nino Fejzibegovic, Carlos Fernández Moro, Lena Klopp-Schulze, Caroline Verbeke, J-Matthias Löhr, Rainer L Heuchel
Chronic pancreatitis is the most common disease of the exocrine pancreas, characterized by progressive inflammation, acinar atrophy and fibrosis. Transforming growth factor-β signaling (TGFβ) is the most potent fibrogenic cytokine known, and its increased expression is a common denominator for fibrosis in chronic pancreatitis. Smad7 is induced by the TGFβ superfamily members as an intracellular inhibitory feedback antagonizing TGFβ signaling. To investigate the functional role of Smad7 in vivo, we induced chronic pancreatitis by repeated administration of cerulein in mice that are deficient in exon-I of Smad7...
September 2016: Biochimica et Biophysica Acta
Maximilianos Elkouris, Haroula Kontaki, Athanasios Stavropoulos, Anastasia Antonoglou, Kostas C Nikolaou, Martina Samiotaki, Eszter Szantai, Dimitra Saviolaki, Peter J Brown, Paschalis Sideras, George Panayotou, Iannis Talianidis
TGF-β signaling regulates a variety of cellular processes, including proliferation, apoptosis, differentiation, immune responses, and fibrogenesis. Here, we describe a lysine methylation-mediated mechanism that controls the pro-fibrogenic activity of TGF-β. We find that the methyltransferase Set9 potentiates TGF-β signaling by targeting Smad7, an inhibitory downstream effector. Smad7 methylation promotes interaction with the E3 ligase Arkadia and, thus, ubiquitination-dependent degradation. Depletion or pharmacological inhibition of Set9 results in elevated Smad7 protein levels and inhibits TGF-β-dependent expression of genes encoding extracellular matrix components...
June 21, 2016: Cell Reports
Chao Yan, Li-Ping Shen, Rui Ma, Bo Li, Xiang-Yang Li, Hui Hua, Bo Zhang, Qian Yu, Yu-Gang Wang, Ren-Xian Tang, Kui-Yang Zheng
Clonorchis sinensis (C. sinensis) infection can lead to biliary fibrosis. MicroRNAs (miRNAs) play important roles in regulation of genes expression in the liver diseases. However, the differential expression of miRNAs that probably regulates the portal fibrogenesis caused by C. sinensis has not yet been investigated. Hepatic miRNAs expression profiles from C. sinensis-infected mice at different time-points were analyzed by miRNA microarray and validated by quantitative real-time PCR (qRT-PCR). 349 miRNAs were differentially expressed in the liver of the C...
September 2016: Infection, Genetics and Evolution
Guangzao Li, Renpeng Zhou, Qi Zhang, Banghong Jiang, Qingkai Wu, Chen Wang
Hypertrophic scar (HS) is a fibroproliferative disorder caused by abnormal wound healing, which is characterized by excessive deposition of extracellular matrix (ECM) secreted by fibroblasts. We previous have found that expression of microRNA-21(miR-21) was increased in tissues and fibroblasts of HS. However, the underlying molecular mechanism remains to be further elucidated. In this study, we identified the miR-21 was a marker for the phenotype of HS fibroblasts, as anti-miR-21 reduced expression of fibrosis markers such as Col1A1, Col3A1, Fn and α-SMA in fibroblasts and overexpression of miR-21 promoted fibroproliferative expression in fibroblasts...
July 1, 2016: Experimental Cell Research
Ok-Seon Kwon, Keun-Tae Kim, Eunioo Lee, Myoungjae Kim, Seo-Hyun Choi, Henghong Li, Albert J Fornace, Jae-Ho Cho, Yun-Sil Lee, Ji-Seon Lee, Yoon-Jin Lee, Hyuk-Jin Cha
Radiation-induced lung fibrosis, the most serious effect of lung cancer radiotherapy on normal tissue, remains a major technical obstacle to the broader application of radiotherapy to patients with lung cancer. This study describes the use of an image-guided irradiation system in mice mimicking stereotactic body radiotherapy (SBRT) to examine the molecular features of chronic fibrotic response after radiation injury. MicroRNA (miR) array analysis of injured pulmonary tissue identified a set of miRs whose expression was significantly increased in damaged lung tissue...
2016: PloS One
Jie Zhao, Li Wang, Ai-Li Cao, Ming-Qian Jiang, Xia Chen, Yi Wang, Yun-Man Wang, Hao Wang, Xue-Mei Zhang, Wen Peng
OBJECTIVE: Traditional Chinese Medicine compound HuangQi decoction is widely used in clinical treatment of chronic kidney disease, but its role on renal interstitial fibrosis and the underlying mechanism remains unclear. The aim of this study is to investigate the effect of HuangQi decoction on renal interstitial fibrosis and its association with the TGF-β/Smad signaling pathway Methods: A total of 120 C57/BL mice were randomly divided into six groups: sham group, sham plus high-dose HuangQi decoction (1...
2016: Cellular Physiology and Biochemistry
Yu Ji, Yan-Nong Dou, Qian-Wen Zhao, Ji-Zhou Zhang, Yan Yang, Ting Wang, Yu-Feng Xia, Yue Dai, Zhi-Feng Wei
AIM: Paeoniflorin has shown to attenuate bleomycin-induced pulmonary fibrosis (PF) in mice. Because the epithelial-mesenchymal transition (EMT) in type 2 lung endothelial cells contributes to excessive fibroblasts and myofibroblasts during multiple fibrosis of tissues, we investigated the effects of paeoniflorin on TGF-β mediated pulmonary EMT in bleomycin-induced PF mice. METHODS: PF was induced in mice by intratracheal instillation of bleomycin (5 mg/kg). The mice were orally treated with paeoniflorin or prednisone for 21 d...
June 2016: Acta Pharmacologica Sinica
Xiangbin Xiao, Guanglei Chang, Jian Liu, Guangyun Sun, Li Liu, Shu Qin, Dongying Zhang
Statins are widely used in patients with cardiovascular diseases. A considerable number of previous studies revealed that the intracellular signaling of transforming growth factor (TGF)‑β1 mediated the development of cardiomyocyte hypertrophy and interstitial fibrosis. However, whether statins can ameliorate ventricular remodeling in post‑myocardial infarction via the TGF‑β1 signaling pathway remains to be rigorously tested. The left anterior descending artery was ligated to induce a rat model of myocardial infarction...
June 2016: Molecular Medicine Reports
Xuyu He, Kunyi Zhang, Xiuren Gao, Liwen Li, Hong Tan, Jiyan Chen, Yingling Zhou
Tachycardia-induced atrial fibrosis is a hallmark of the structural remodeling of atrial fibrillation (AF). The mechanisms underlying tachycardia-induced atrial fibrosis remain unclear. In our previous study, we found that Smad7-downregulation promoted the development of atrial fibrosis in AF. Fibroblasts are enriched in microRNA-21 (miR-21), which contributes to the development of fibrosis and heart failure in the cardiovascular system. Our study was designed to test the hypothesis that miR-21 reinforces the TGF-β1/Smad signaling pathway in AF-induced atrial fibrosis by down-regulating Smad7...
October 2016: Heart and Vessels
Fan Yang, Yao Wang, Jun Xue, Qian Ma, Juan Zhang, Yun-Fei Chen, Zhen-Zhong Shang, Quan-Qiang Li, Shu-Ling Zhang, Lei Zhao
This study sought to investigate the anti-fibrotic effect of Corilagin via interference with the miR-21/smad7/ERK signaling pathway in a schistosomiasis-induced hepatic fibrosis mouse model. Mice were infected with Schistosoma japonicum cercaria to establish the mouse model of schistosomiasis-induced hepatic fibrosis. At four weeks after infection, the groups were given different medications. The living conditions were observed. Real-time PCR was employed to detect the mRNA levels of miR-21, smad7 and connective tissue growth factor (CTGF), and western blotting was used to examine the protein levels of smad7, CTGF, smad1, p-smad1, smad2, p-smad2, ERK1/2, p-ERK1/2 and TGF-β receptor I...
August 2016: Parasitology International
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