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Toshiaki Tanaka, Kaoru Goto, Mitsuyoshi Iino
Sec8 is one of the subunits of the exocyst, which is an evolutionarily conserved complex of eight proteins, comprising Sec3 (EXOC1), Sec5 (EXOC2), Sec6 (EXOC3), Sec8 (EXOC4), Sec10 (EXOC5), Sec15 (EXOC6), Exo70 (EXOC7), and Exo84 (EXOC8) subunits. Sec8 knockout mice embryos initiate gastrulation but are unable to progress beyond the primitive streak stage and die shortly. During embryonic development, the first epithelial-mesenchymal transition (EMT) event occurs at gastrulation. Sec8 may be involved in the early embryonic development through EMT...
October 18, 2016: Cellular Signalling
Olga Ruiz-Andres, Maria Dolores Sanchez-Niño, Juan Antonio Moreno, Marta Ruiz-Ortega, Adrian Mario Ramos, Ana Belén Sanz, Alberto Ortiz
Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR)...
October 19, 2016: American Journal of Physiology. Renal Physiology
Tian Yang, Jinyuan Wang, Yamei Pang, Xiaomin Dang, Hui Ren, Ya Liu, Mingwei Chen, Dong Shang
Pulmonary silicosis is characterized by lung fibrosis, which leads to impairment of pulmonary function; the specific mechanism remains to be fully elucidated Emodin shows antifibrotic effects in several organs with fibrosis, however, it has not been investigated in pulmonary silicosis. In the present study, the possible mechanism of lung fibrosis and the antifibrotic effect of emodin in silica inhalation‑induced lung fibrosis were investigated. Pulmonary silica particle inhalation was used to induce lung fibrosis in mice...
October 12, 2016: Molecular Medicine Reports
Marie-Noëlle Labour, Mathieu Riffault, Søren T Christensen, David A Hoey
The recruitment of mesenchymal stem cells (MSCs) is a crucial process in the development, maintenance and repair of tissues throughout the body. Transforming growth factor-β1 (TGFβ1) is a potent chemokine essential for the recruitment of MSCs in bone, coupling the remodelling cycle. The primary cilium is a sensory organelle with important roles in bone and has been associated with cell migration and more recently TGFβ signalling. Dysregulation of TGFβ signalling or cilia has been linked to a number of skeletal pathologies...
October 17, 2016: Scientific Reports
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
R D Chavez, G Coricor, J Perez, H-S Seo, R Serra
OBJECTIVE: We previously identified PAPSS2 as a transcriptional target of TGF-β in chondrocytes. PAPSS2 is required for proper sulfation of proteoglycans in cartilage. Defective sulfation in the matrix results in alterations in mechanical properties of the cartilage that would be expected to result in degeneration. The objective of this study was to identify factors that regulate PAPSS2 expression and compare to a known TGF-β responsive gene, PRG4. In this study, TGF-β-mediated regulation of SOX9 was characterized, and the involvement of SOX9 in regulation of PAPSS2 mRNA was investigated...
October 13, 2016: Osteoarthritis and Cartilage
Veenu Tripathi, Katherine M Sixt, Shaojian Gao, Xuan Xu, Jing Huang, Roberto Weigert, Ming Zhou, Ying E Zhang
In advanced stages of cancers, TGF-β promotes tumor progression in conjunction with inputs from receptor tyrosine kinase pathways. However, mechanisms that underpin the signaling cooperation and convert TGF-β from a potent growth inhibitor to a tumor promoter are not fully understood. We report here that TGF-β directly regulates alternative splicing of cancer stem cell marker CD44 through a phosphorylated T179 of SMAD3-mediated interaction with RNA-binding protein PCBP1. We show that TGF-β and EGF respectively induce SMAD3 and PCBP1 to colocalize in SC35-positive nuclear speckles, and the two proteins interact in the variable exon region of CD44 pre-mRNA to inhibit spliceosome assembly in favor of expressing the mesenchymal isoform CD44s over the epithelial isoform CD44E...
October 4, 2016: Molecular Cell
Dan Ouyang, Lifeng Xu, Lihua Zhang, Dongguang Guo, Xiaotong Tan, Xiaofang Yu, Junjie Qi, Yaqiong Ye, Qihong Liu, Yongjiang Ma, Yugu Li
MicroRNAs are highly conserved non-coding small RNAs participating in almost all kinds of biological activities. MiR-181a has been reported to be involved in the differentiation of porcine primary preadipocytes, but the profound effect of miR-181a-5p on 3T3-L1 adipocyte differentiation and proliferation is still unclear. In this study, we found that supplementation of miR-181a-5p in 3T3-L1 cells significantly promoted the adipogenesis and inhibited cell proliferation with increased expression of adipogenic marker genes including peroxisome proliferator-activated receptor gamma (Pparγ), CCAAT/enhancer-binding protein alpha (C/ebpα), fatty acid-binding protein 4 (Fabp4), and Adiponectin, accompanied by an accumulation of lipid droplet, an increase of triglyceride content, and a decrease of cell proliferation...
October 14, 2016: Acta Biochimica et Biophysica Sinica
Weiguang Wang, Buer Song, Teni Anbarchian, Anna Shirazyan, Joshua E Sadik, Karen M Lyons
TGFβs act through canonical and non-canonical pathways, and canonical signals are transduced via Smad2 and Smad3. However, the contribution of canonical vs. non-canonical pathways in cartilage is unknown because the role of Smad2 in chondrogenesis has not been investigated in vivo. Therefore, we analyzed mice in which Smad2 is deleted in cartilage (Smad2CKO), global Smad3-/- mutants, and crosses of these strains. Growth plates at birth from all mutant strains exhibited expanded columnar and hypertrophic zones, linked to increased proliferation in resting chondrocytes...
October 2016: PLoS Genetics
Bernardo Sousa-Pinto, Laura Gonçalves, Adriana R Rodrigues, Inês Tomada, Henrique Almeida, Delminda Neves, Alexandra M Gouveia
Transforming growth factor beta (TGF-β) plays an important role in the pathogenesis of obesity, influencing the release of inflammation mediators and promoting remodeling and collagen deposition in the adipose tissue (AT). In this context, this work aims to elucidate whether TGF-β and Smad-dependent or Smad-independent signaling pathways contribute to regional differentiation of AT in high-fat diet (HFD) and energy-restricted (ER) rat models. For this, TGF-β, TGF-β receptors I and II, PAI-1 and GLUT4 mRNA levels were quantified by real-time PCR, and western blotting assays allowed the semiquantification of TGF-β and proteins from Smad3, ERK1/2 and Akt signaling pathways in subcutaneous and visceral (epididymal, retroperitoneal and mesenteric) fat depots from control, HFD and ER-treated rats...
August 26, 2016: Journal of Nutritional Biochemistry
J Wang, Y Qiu, N-W Shi, J-N Zhao, Y-C Wang, H Jiang, H-B Qian
OBJECTIVE: The aim of this study was to investigate the molecular mechanism into the keratinocyte migration, which is promoted by Transforming growth factor-β1 (TGF-β1) during wound healing. MATERIALS AND METHODS: In the present study, we investigated the regulation by TGF-β1 on phosphatase and tensin homolog (PTEN) expression, and microRNA-21 (miR-21) level with real-time quantitative PCR or/and Western blotting, and then examined the regulatory role of miR-21 on the PTEN expression and the mesenchymal transition, with real-time quantitative PCR, western blotting and luciferase reporter assay, and the migration of keratinocytic HaCaT cells with scratch assay...
September 2016: European Review for Medical and Pharmacological Sciences
Bo Wu, Bomin Guo, Jie Kang, Xianzhao Deng, Youben Fan, Xiaoping Zhang, Kaixing Ai
Smad ubiquitin regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that regulates transforming growth factor β (TGF-β)/Smad signaling and is implicated in a wide range of cellular responses. However, the exact mechanism whereby Smurf2 controls TGF-β-induced signaling pathways remains unknown. Here, we identified the relationship between the alternate TGF-β signaling pathways: TGF-β/PI3K/Akt/β-catenin and TGF-β/Smad2/3/FoxO1/PUMA and Smurf2. The results showed that TGF-β promoted proliferation, invasion, and migration of human pancreatic carcinoma (PANC-1) cells through the PI3K/Akt/β-catenin pathway...
October 11, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Florian S Schoenhoff
No abstract text is available yet for this article.
October 5, 2016: EBioMedicine
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
Y H Xie, X P Li, Z X Xu, P Qian, X L Li, Y Q Wang
In this research, compound Maqin decoction (CMD) has been shown to positively affect in airway inflammation of asthma models. We evaluated the effects of CMD on the expression of transforming growth factor (TGF)-β1/Smad proteins, interleukin (IL)-17, and IL-10 in lung tissue of asthmatic rats. Asthma was induced in a rat model using ovalbumin. After a 4-week treatment with CMD, rats were killed to evaluate the expression of TGF-β1 and Smad proteins in lung tissue. IL-10 and IL-17 levels in lung tissue homogenates were determined by ELISA...
September 2, 2016: Genetics and Molecular Research: GMR
W Gao, R Su, W Sun, Q Z Wang, X Y Lv, J J Bao, J R Yu, L H Wang, H H Musa, L Chen
The temporal and spatial patterns of Smad and Yes-associated protein 1 (YAP1) expression were investigated in skeletal muscle (gastrocnemius muscle and extensor digitorum longus) at different growth stages (2 days old, 2 and 6 months old) in Hu sheep. Smads were differentially expressed in sheep skeletal muscle, with high expression in the gastrocnemius muscle and lower expression in the extensor digitorum longus. Expression of Smad2, Smad3, and Smad4 at the 2-day-old stage was significantly higher than at other stages (P < 0...
August 26, 2016: Genetics and Molecular Research: GMR
Kaveh Daneshvar, Joshua V Pondick, Byeong-Moo Kim, Chan Zhou, Samuel R York, Jillian A Macklin, Ameed Abualteen, Bo Tan, Alla A Sigova, Chelsea Marcho, Kimberly D Tremblay, Jesse Mager, Michael Y Choi, Alan C Mullen
Long noncoding RNAs (lncRNAs) exhibit diverse functions, including regulation of development. Here, we combine genome-wide mapping of SMAD3 occupancy with expression analysis to identify lncRNAs induced by activin signaling during endoderm differentiation of human embryonic stem cells (hESCs). We find that DIGIT is divergent to Goosecoid (GSC) and expressed during endoderm differentiation. Deletion of the SMAD3-occupied enhancer proximal to DIGIT inhibits DIGIT and GSC expression and definitive endoderm differentiation...
October 4, 2016: Cell Reports
Xinxin Du, Yuezhong Liu, Jinxiang Liu, Quanqi Zhang, Xubo Wang
Following the two rounds of whole-genome duplication (WGD) during deuterosome evolution, a third genome duplication occurred in the ray-fined fish lineage and is considered to be responsible for the teleost-specific lineage diversification and regulation mechanisms. As a receptor-regulated SMAD (R-SMAD), the function of SMAD3 was widely studied in mammals. However, limited information of its role or putative paralogs is available in ray-finned fishes. In this study, two SMAD3 paralogs were first identified in the transcriptome and genome of Japanese flounder (Paralichthys olivaceus)...
2016: PeerJ
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
Lichan Tao, Yihua Bei, Ping Chen, Zhiyong Lei, Siyi Fu, Haifeng Zhang, Jiahong Xu, Lin Che, Xiongwen Chen, Joost Pg Sluijter, Saumya Das, Dragos Cretoiu, Bin Xu, Jiuchang Zhong, Junjie Xiao, Xinli Li
Dysregulation of microRNAs has been implicated in many cardiovascular diseases including fibrosis. Here we report that miR-433 was consistently elevated in three models of heart disease with prominent cardiac fibrosis, and was enriched in fibroblasts compared to cardiomyocytes. Forced expression of miR-433 in neonatal rat cardiac fibroblasts increased proliferation and their differentiation into myofibroblasts as determined by EdU incorporation, α-SMA staining, and expression levels of fibrosis-associated genes...
2016: Theranostics
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