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Smad7 AND Fibrosis

Sang Woo Park, Jaehoon Choi, Junhyung Kim, Woohhyeok Jeong, Jun Sik Kim, Bae Kwon Jeong, Sung Chul Shin, Jin Hee Kim
The aim of this study was to evaluate the protective effects of anthocyanins from the black soybean seed coat against radiation injury in dermal fibroblasts and mouse skin. Dermal fibroblasts treated with 50 and 100 µg/mL anthocyanins were irradiated with single doses of 20 Gy. Cell viability, intracellular reactive oxygen species (ROS) production, and mRNA expression were measured. A total of 60 mice were used for an in vivo study. A dose of 100 µg/mL anthocyanins was administered daily for 5 days before or after radiation therapy...
March 19, 2018: Archives of Dermatological Research
Zezhao Li, Zhen Hong, Zhiqing Peng, Yongcai Zhao, Rusheng Shao
Diabetic nephropathy (DN) is the major cause of end-stage renal disease in diabetic patients. Zicao, a well-known Chinese traditional medicine, has attracted much attention due to its beneficial effects in various medical fields. In this study, we attempted to investigate the effects and mechanisms of action of acetylshikonin, the main ingredient of Zicao, on renal dysfunction in DN. Our results showed that administration with acetylshikonin not only decreased blood urea nitrogen, urine creatinine and the mean kidney-to-body weight ratio in streptozotocin-induced diabetic mice, but also restored the loss of body weight, whereas the blood glucose was not changed...
March 17, 2018: Human Cell
Shouzhe Lin, Dameng Lian, Weihua Liu, Aaron Haig, Ian Lobb, Ahmed Hijazi, Hassan Razvi, Jeremy Burton, Matthew Whiteman, Alp Sener
OBJECTIVES: To assess the effects of slow-releasing H2 S donor GYY4137 on post-obstructive renal function and injury following unilateral ureteral obstruction (UUO) by using the UUO and reimplantation (UUO-R) model in rats and to elucidate potential mechanisms by using an in vitro model of epithelial-mesenchymal transition (EMT). METHODS: Male Lewis rats underwent UUO at the left ureterovesical junction. From post-obstructive day (POD) 1-13, rats received daily intraperitoneal (IP) injection of phosphate buffered saline (PBS, 1 mL) or GYY4137 (200 μmol/kg/day in 1 mL PBS, IP)...
March 6, 2018: Nitric Oxide: Biology and Chemistry
Lin Chen, Tian Yang, De-Wen Lu, Hui Zhao, Ya-Long Feng, Hua Chen, Dan-Qian Chen, Nosratola D Vaziri, Ying-Yong Zhao
Chronic kidney disease (CKD) has emerged as a major cause of morbidity and mortality worldwide. Interstitial fibrosis, glomerulosclerosis and inflammation play the central role in the pathogenesis and progression of CKD to end stage renal disease (ESRD). Transforming growth factor-β1 (TGF-β1) is the central mediator of renal fibrosis and numerous studies have focused on inhibition of TGF-β1 and its downstream targets for treatment of kidney disease. However, blockade of TGF-β1 has not been effective in the treatment of CKD patients...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Anbang Han, Yingdong Lu, Qi Zheng, Jian Zhang, YiZhou Zhao, Mingjing Zhao, Xiangning Cui
BACKGROUND/AIMS: Qiliqiangxin (QL), a traditional Chinese medicine, has been demonstrated to be effective and safe for the treatment of chronic heart failure. Left ventricular (LV) remodeling causes depressed cardiac performance and is an independent determinant of morbidity and mortality after myocardial infarction (MI). Our previous studies have shown that QL exhibits cardiac protective effects against heart failure after MI. The objective of this study was to explore the effects of QL on myocardial fibrosis in rats with MI and to investigate the underlying mechanism of these effects...
February 28, 2018: Cellular Physiology and Biochemistry
Wenzhao Wang, Ronghan Liu, Yanlin Su, Hongfei Li, Wei Xie, Bin Ning
Little regeneration of transected axons occurs after the damage caused by traumatic spinal cord injury (SCI), and unidirectional and irreversible fibrotic scars are thought to be the main chemical and physical obstacle for axonal regrowth in SCI pathology. We previously demonstrated that microRNA (miR)-21-5p and transforming growth factor (TGF)-β1, a central pathological mediator of fibrotic diseases, were significantly up-regulated in the lesion epicenter after SCI. Here, we found that TGF-β1 enhanced miR-21-5p expression in primary spinal fibroblasts, and regulated the expression of fibrosis-related genes...
2018: International Journal of Biological Sciences
Joseph X DiMario
Dystrophic skeletal muscle is characterized by fibrotic accumulation of extracellular matrix components that compromise muscle structure, function, and capacity for regeneration. Tissue fibrosis is often initiated and sustained through transforming growth factor β (TGFβ) signaling, and KLF10 is an immediate early gene that is transcriptionally activated in response to TGFβ signaling. It encodes a transcriptional regulator that mediates the effects of TGFβ signaling in a variety of cell types. This report presents results of investigation of the effects of loss of KLF10 gene expression in wild-type and dystrophic (mdx) skeletal muscle...
February 16, 2018: American Journal of Pathology
Lei Yang, Xingai Jiao, Jinxiang Wu, Jiping Zhao, Tian Liu, Jianfeng Xu, Xiaohui Ma, Liuzao Cao, Lin Liu, Yahui Liu, Jingyu Chi, Minfang Zou, Shuo Li, Jiawei Xu, Liang Dong
Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensi s on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated...
March 2018: Experimental and Therapeutic Medicine
Fang-Hua Qi, Ping-Ping Cai, Xiang Liu, Guo-Min Si
Epithelial-mesenchymal transition (EMT) is a critical step and key factor during renal fibrosis. Preventing renal tubular EMT is important for delaying the progression of chronic kidney disease (CKD). P311, a highly conserved 8-kDa intracellular protein, has been indicated as an important factor in myofibroblast transformation and in the progression of fibrosis. However, the related studies on P311 on renal fibrosis are limited and the mechanisms of P311 in the progression of renal tubulointerstitial fibrosis remain largely unknown...
February 12, 2018: International Journal of Molecular Medicine
Lihua Wei, Shimei Zhao, Gaoxing Wang, Shiming Zhang, Weibo Luo, Zhengxue Qin, Xiongjie Bi, Yimei Tan, Moke Meng, Jun'an Qin, Huiping Qin, Dan Tian, An'wen Zhang
Atherosclerosis is a complicated process comprising inflammation, accumulation of collagen matrix and aberrant DNA methylation. SMAD7 is known to play an important role in fibrosis and inflammation. In recent years, increasing research has concentrated on the connection between DNA methylation and atherosclerosis. The current study was designed to investigate methylation status of some specific gene with a focus on SMAD7 in atherosclerosis and elucidate their relationship. We found that SMAD7 expression was decreased and its promoter region was markedly methylated in atherosclerotic plaques when compared with normal artery walls...
January 20, 2018: Biochemical and Biophysical Research Communications
Qi Sun, Jiao Miao, Jing Luo, Qi Yuan, Hongdi Cao, Weifang Su, Yang Zhou, Lei Jiang, Li Fang, Chunsun Dai, Ke Zen, Junwei Yang
Renal fibrosis is a final common pathway of chronic kidney disease. Sustained activation of fibroblast is considered to play a key role in perpetuating renal fibrosis, but the driving force in the perpetuation stage is only partially understood. To date, some investigations have identified specific overexpression of miR-21 in the progression of kidney fibrosis. Nevertheless, the precise role of miR-21 in fibroblast activation remains largely unknown. In this study, we identified miR-21 was significantly upregulated in activated fibroblasts, and maintained itself at constant high level by employing a miR-21/PDCD4/AP-1 auto-regulatory loop...
January 19, 2018: Journal of Cell Science
Ping Chen, Qihui Luo, Chao Huang, Qi Gao, Like Li, Jingfei Chen, Bing Chen, Wentao Liu, Wen Zeng, Zhengli Chen
OBJECTIVE: This study aimed to investigate the mechanism of the interaction between Yes-associated protein (YAP) and transforming growth factor-β (TGF-β)/Smad signaling pathways in the development of non-alcoholic fatty liver disease (NAFLD). METHODS: Serum samples of monkeys with biopsy-proven NAFLD and healthy normal monkeys were used to measure fasting plasma glucose (FPG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG) and albumin (ALB) with the BECKMAN CX5 PRO...
January 12, 2018: Hepatology International
Libin Ma, Hua Li, Shuchao Zhang, Xiaoling Xiong, Kean Chen, Peiwu Jiang, Kang Jiang, Gang Deng
BACKGROUND: Emodin is a natural active component extracted from Chinese herbs. In this study, we investigated the therapeutic effect of emodin on surgery-induced renal fibrosis in rat. Moreover, the function of Smad ubiquitination regulatory factor 2 (Smurf 2) was further studied in vitro. METHODS: The renal fibrosis rat model was established via 5/6 renal mass reduction. The histopathological abnormalities of renal tissues in rats were tested via staining method and microscopic examination...
February 2018: International Urology and Nephrology
Pengbo Wang, Lin Luo, Qiusheng Shen, Gaoyong Shi, Anaz Mohammed, Songshi Ni, Xiang Wu
Left ventricular hypertrophy is more commonly associated with hemodynamic overload imposed by hypertension or volume overload. Transforming growth factor β (TGF-β) is involved in the cardiac hypertrophy and fibrosis of the left ventricle. The fact that TGF-β1 and the nuclear factor erythroid 2-related factor 2 (Nrf2) both become up-regulated upon persistent vessel overload suggests that these two factors may virtually impact on their signaling pathways. In this research, 40 rats were divided into sham group, model group, rosuvastatin low and high dose group...
February 5, 2018: European Journal of Pharmacology
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Radiation therapy induces DNA damage and inflammation leading to fibrosis. Fibrosis can occur 4 to 12 months after radiation therapy. This process worsens with time and years. Radiation-induced fibrosis is characterized by fibroblasts proliferation, myofibroblast differentiation, and synthesis of collagen, proteoglycans and extracellular matrix. Myofibroblasts are non-muscle cells that can contract and relax. Myofibroblasts evolve towards irreversible retraction during fibrosis process. In this review, we discussed the interplays between transforming growth factor-β1 (TGF-β1), canonical WNT/β-catenin pathway and peroxisome proliferator-activated receptor gamma (PPAR γ) in regulating the molecular mechanisms underlying the radiation-induced fibrosis, and the potential role of PPAR γ agonists...
October 27, 2017: Oncotarget
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...
January 2018: Molecular Medicine Reports
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...
January 2018: Molecular Medicine Reports
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
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
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
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