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Smad3 AND Beta cells

Yuhee Ryu, Li Jin, Hae Jin Kee, Zhe Hao Piao, Jae Yeong Cho, Gwi Ran Kim, Sin Young Choi, Ming Quan Lin, Myung Ho Jeong
Gallic acid, a type of phenolic acid, has been shown to have beneficial effects in inflammation, vascular calcification, and metabolic diseases. The present study was aimed at determining the effect and regulatory mechanism of gallic acid in cardiac hypertrophy and fibrosis. Cardiac hypertrophy was induced by isoproterenol (ISP) in mice and primary neonatal cardiomyocytes. Gallic acid pretreatment attenuated concentric cardiac hypertrophy. It downregulated the expression of atrial natriuretic peptide, brain natriuretic peptide, and beta-myosin heavy chain in vivo and in vitro...
October 5, 2016: Scientific Reports
Lucy Cassar, Craig Nicholls, Alex R Pinto, Ruping Chen, Lihui Wang, He Li, Jun-Ping Liu
Human telomerase reverse transcriptase (hTERT) plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 (BMP7) induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis...
September 30, 2016: Protein & Cell
Xin Fang, Yang Gao, Qinglei Li
Ovarian granulosa cell tumors (GCTs) are rare gynecologic tumors in women. Due to the rarity and limited research efforts invested, the etiology of GCTs remains poorly defined. A landmark study has discovered the mutation of forkhead box L2 (FOXL2) as a genetic hallmark of adult GCTs in the human. However, our understanding of the role of cell signaling in GCT development is far from complete. Increasing lines of evidence highlight the importance of TGF-beta (TGFB) superfamily signaling in the pathogenesis of GCTs...
September 28, 2016: Biology of Reproduction
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
Xinru Zhou, Yong Mao, Jianjie Zhu, Fanyi Meng, Qi Chen, Lihua Tao, Rui Li, Fengqing Fu, Cuiping Liu, Yuanjia Hu, Weipeng Wang, Hongjian Zhang, Dong Hua, Weichang Chen, Xueguang Zhang
Transforming growth factor-beta 1 (TGF-β1) suppresses T cell function, promoting tumor immune escape. Yet, whether the depression of TGF-β1 on T cell function is mediated by co-inhibitory molecules B7-H3 and B7-H4 remains largely unclear. Here, we demonstrated that TGF-β1 elevated the expression of miR-155 in colorectal cancer cells through SMAD3 and SMAD4. The upregulated miR-155 attenuated miR-143 by inhibiting its direct target, the transcription factor CEBPB. Consequently, the direct target genes of miR-143, B7-H3 and B7-H4, were augmented in the cytoplasm and membrane of tumor cells...
September 10, 2016: Oncotarget
Meredith L Sosulski, Rafael Gongora, Carol Feghali-Bostwick, Joseph A Lasky, Cecilia G Sanchez
Oxidative stress leads to alveolar epithelial cell injury and fibroblast-myofibroblast differentiation (FMD), key events in the pathobiology of pulmonary fibrosis (PF). Sirtuin 3 (SIRT3) is a mitochondrial protein deacetylase regulator of antioxidant response and mitochondrial homeostasis. Here, we demonstrate reduced SIRT3 expression in the lungs of old mice compared to young mice, as well as in two murine models of PF. The analysis of the pattern of SIRT3 expression in the lungs of patients with PF revealed low SIRT3 staining within the fibrotic regions...
August 13, 2016: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Silke Leiting, Sebastian Seidl, Adoracion Martinez-Palacian, Lars Muhl, Sandip M Kanse
Deletion of the Habp2 gene encoding Factor VII-activating protease (FSAP) increases liver fibrosis in mice. A single nucleotide polymorphism (G534E) in HABP2 leads to lower enzymatic activity and is associated with enhanced liver fibrosis in humans. Liver fibrosis is associated with a decrease in FSAP expression but, to date, nothing is known about how this might be regulated. Primary mouse hepatocytes or the hepatocyte cell line, AML12, were treated with different factors, and expression of FSAP was determined...
September 30, 2016: Journal of Biological Chemistry
A R Garcia-Rendueles, J S Rodrigues, M E R Garcia-Rendueles, M Suarez-Fariña, S Perez-Romero, F Barreiro, I Bernabeu, J Rodriguez-Garcia, L Fugazzola, T Sakai, F Liu, J Cameselle-Teijeiro, S B Bravo, C V Alvarez
Papillary thyroid carcinoma (PTC), the most frequent thyroid cancer, is characterized by low proliferation but no apoptosis, presenting frequent lymph-node metastasis. Papillary thyroid carcinoma overexpress transforming growth factor-beta (TGF-β). In human cells, TGF-β has two opposing actions: antitumoral through pro-apoptotic and cytostatic activities, and pro-tumoral promoting growth and metastasis. The switch converting TGF-β from a tumor-suppressor to tumor-promoter has not been identified. In the current study, we have quantified a parallel upregulation of TGF-β and nuclear p27, a CDK2 inhibitor, in samples from PTC...
July 25, 2016: Oncogene
Dongguang Guo, Yaqiong Ye, Junjie Qi, Lihua Zhang, Lifeng Xu, Xiaotong Tan, Xiaofang Yu, Qihong Liu, Jilong Liu, Yuan Zhang, Yongjiang Ma, Yugu Li
The expression profiles of miRNAs in thymus tissues from mice of different age have been demonstrated in our previous study. After an integrated analysis of the miRNA expression profiles, we demonstrated that the expression of miR-181a-5p was significantly decreased in thymic epithelial cells (TECs) from 10- to 19-month-old mice when compared with that in TECs from 1-month-old mice by quantitative reverse transcriptase polymerase chain reaction. We hypothesized that miR-181a-5p in TECs might be associated with the age-related thymus involution through regulating some genes or signaling pathway...
September 2016: Acta Biochimica et Biophysica Sinica
Shih-Ping Liu, Chen-Huan Lin, Shao-Ji Lin, Ru-Huei Fu, Yu-Chuen Huang, Shih-Yin Chen, Shinn-Zong Lin, Chung Y Hsu, Woei-Cherng Shyu
Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) are capable of self-renewal and differentiation into any cell type, thus making them the focus of many clinical application studies. Culturing ESCs on mouse embryonic fibroblast-derived and cell-based feeder layers to maintain pluripotency is a standard laboratory procedure. However, xenogeneic contamination and the large amount of time required for feeder cell preparation are two challenges that encourage the use of a murine-based feeder layer...
April 2016: Journal of Biomedical Nanotechnology
Shukun Zhang, Menglan Zhang, Hong Huang, Shiying Zhou, Yanshneg Du, Xin Yi, Junming Luo
This study aimed at evaluating the effect of high glucose on the expression of extracellular matrix (ECM) protein Matrilin-2 and the mechanism underlying this effect by using a mouse mesangial cell line. Mouse mesangial cells (MMCs) were cultured in media containing normal (5 mM d-glucose) or high concentrations of glucose (30 mM d-glucose). The expression of Matrilin-2 was assessed by either RT-PCR or western blot. Additionally, transforming growth factor beta 1 (TGF-β1) inhibitors and TGF-β1 were used to determine whether glucose-regulated Matrilin-2 expression was mediated by the TGF-β1/Smad3 signaling pathway...
May 27, 2016: Biochemical and Biophysical Research Communications
Yifu Sun, Peng Xia, Haipeng Zhang, Biao Liu, Ying Shi
Osteosarcoma is the most common type of aggressive bone cancer. Current treatment strategies include surgical resection, radiation, and chemotherapy. Doxorubicin has been widely used as a chemotherapeutic drug to treat osteosarcoma. However, drug resistance has become a challenge to its use. In this study, p53-wild type U2OS and p53-null MG-63 osteosarcoma-derived cells were used to investigate the mechanism of doxorubicin-induced cytotoxicity. In cell viability assays, doxorubicin effectively induced apoptosis in U2OS cells via the p53 signaling pathway, evidenced by elevated PUMA and p21 protein levels and activated caspase 3 cleavage...
2016: American Journal of Cancer Research
Jessica A Zagory, Marie V Nguyen, William Dietz, Nirmala Mavila, Allison Haldeman, Anatoly Grishin, Kasper S Wang
BACKGROUND: In biliary atresia (BA), epithelial-mesenchymal hepatic progenitor cells (HPC) expressing the stem/progenitor cell marker PROMININ-1 (PROM1) undergo expansion and subsequent transdifferentiation into collagen-producing myofibroblasts within regions of evolving biliary fibrosis under the regulation of Transforming Growth Factor-β (TGFβ) signaling. We hypothesized that pro-inflammatory Toll-like Receptor-3 (TLR3) signal activation promotes the differentiation of PROM1+ HPC via TGFβ pathway activation in vitro...
June 2016: Journal of Pediatric Surgery
Meisam Jafarzadeh, Bahram M Soltani
OBJECTIVE: SMAD proteins are the core players of the transforming growth factor-beta (TGFβ) signaling pathway, a pathway which is involved in cell proliferation, differentiation and migration. On the other hand, hsa-miRNA-590-5p (miR-590-5p) is known to have a negative regulatory effect on TGFβ signaling pathway receptors. Since, RNAhybrid analy- sis suggested SMAD3 as a bona fide target gene for miR-590, we intended to investigate the effect of miR-590-5p on SMAD3 transcription. MATERIALS AND METHODS: In this experimental study, miR-590-5p was overexpressed in different cell lines and its increased expression was detected through quantitative reverse transcription-polymerase chain reaction (RT-qPCR)...
2016: Cell Journal
Liping Feng, Friederike L Jayes, Lauren Nc Johnson, David W Schomberg, Phyllis C Leppert
Utilizing both primary myometrial cells and a myometrial cell line, we show here that myometrial cells undergo transition to a myofibroblast-like phenotype after a biological insult of 72 hours serum starvation and serum add-back (SB: 1% to 10% FBS). We also found that thrombospondin-1 was increased and that the transforming growth factor-beta (TGFB)-SMAD3/4 pathway was activated. This pathway is a key mediator of fibrosis and extracellular matrix (ECM) deposition. Applying the same insult supplemented with TGFB3 (1-10ng/ml) and ascorbic acid (100µg/ml) in the serum add-back treatment, we further demonstrated that cells migrated into nodules containing collagen and fibronectin...
March 22, 2016: Current Protein & Peptide Science
Sangeeta Dhawan, Ercument Dirice, Rohit N Kulkarni, Anil Bhushan
Diabetes is associated with loss of functional pancreatic β-cells, and restoration of β-cells is a major goal for regenerative therapies. Endogenous regeneration of β-cells via β-cell replication has the potential to restore cellular mass; however, pharmacological agents that promote regeneration or expansion of endogenous β-cells have been elusive. The regenerative capacity of β-cells declines rapidly with age, due to accumulation of p16(INK4a), resulting in limited capacity for adult endocrine pancreas regeneration...
May 2016: Diabetes
Chunyou Wang, Pian Liu, Heshui Wu, Pengfei Cui, Yongfeng Li, Yao Liu, Zhiqiang Liu, Shanmiao Gou
Pancreatic ductal adenocarcinoma (PDAC), which accounts for 96% of all pancreatic cancer cases, is characterized by rapid progression, invasion and metastasis. Transforming growth factor-beta (TGF-β) signaling is an essential pathway in metastatic progression and microRNAs (miRNA) play central roles in the regulation of various biological and pathologic processes including cancer metastasis. However, the molecular mechanisms involved in regulation of miRNAs and activation of TGF-β signaling in PDAC remain to be established...
March 22, 2016: Oncotarget
Naoshi Ikegawa, Takahisa Sasho, Satoshi Yamaguchi, Masahiko Saito, Ryuichiro Akagi, Yuta Muramatsu, Yorikazu Akatsu, Taisuke Fukawa, Koichi Nakagawa, Arata Nakajima, Takane Suzuki, Kazuhisa Takahashi
PURPOSE: Our previous study showed that partial-thickness articular cartilage defects (PTCDs) created in immature rats spontaneously healed to resemble normal hyaline cartilage, but that of mature rats did not. To identify molecules involved in the spontaneous cartilage repair observed in this model, gene expression was compared between PTCD and sham-operated cartilage of immature and mature rats. MATERIALS AND METHODS: Six sets of gene comparisons were made at 12, 24, and 48 hours after the creation of PTCDs in immature and mature rats using microarrays...
May 2016: Connective Tissue Research
Yang Li, Xianfeng Zhang, Dawei Chen, Chengyuan Ma
It has been shown that let-7a was associated with the tumorigenesis of glioma. Our study was designed to infer how let-7a targets high-mobility AT-hook 2 (HMGA2) and suppresses glioma cell proliferation, invasion, and migration. Glioma tissues from 60 glioma patients and 10 normal brain tissues were collected in this study. Real-time quantitative reverse transcription-PCR (qRT-PCR) and in situ hybridization were used to detect the expression levels of let-7a in tissues and cells. The HMGA2 and the proteins related to transforming growth factor-beta (TGF-β)/Smad3 signaling pathway were measured by immunohistochemistry and western blot...
June 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Fu-rong Wu, Ling Jiang, Xiao-li He, Peng-li Zhu, Jun Li
Liver fibrosis is a common pathological process for chronic liver injury caused by multiple etiological factors and an inevitable phase leading to liver cirrhosis. According to the previous studies, hesperidin (HDN) shows a very good protective effect on CCl4-induced chemical hepatic fibrosis in rats. In this experiment, based on the findings of the previous studies, a platelet-derived growth factor (PDGF)-induced HSC-T6 model was established to observe the inhibitory effect of HDN on HSC-T6 proliferation. The ELISA method was adopted to detect the content of collagen I in HSC-T6 supernatant...
July 2015: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
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