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TGF beta activation

Takahiko Niwa, Yasuo Yamakoshi, Hajime Yamazaki, Takeo Karakida, Risako Chiba, Jan C-C Hu, Takatoshi Nagano, Ryuji Yamamoto, James P Simmer, Henry C Margolis, Kazuhiro Gomi
Transforming growth factor-beta (TGF-β) is critical for cell proliferation and differentiation in dental pulp. Here, we show the dynamic mechanisms of TGF-β in porcine dental pulp, odontoblasts and dentin. The mRNA of latent TGF-β1 and TGF-β3 is predominantly expressed in odontoblasts, whereas the mRNA expression level of latent TGF-β2 is high in dental pulp. TGF-β1 is a major isoform of TGF-β, and latent TGF-β1, synthesized in dental pulp, is primarily activated by matrix metalloproteinase 11 (MMP11)...
March 13, 2018: Scientific Reports
Yan Sun, Xiao-Li Liu, Dai Zhang, Fang Liu, Yu-Jing Cheng, Yue Ma, Yu-Jie Zhou, Ying-Xin Zhao
BACKGROUND: Intraplaque angiogenesis, the process of generating new blood vessels mediated by endothelial cells, contributes to plaque growth, intraplaque hemorrhage, and thromboembolic events. Platelet-derived exosomes (PLT-EXOs) affect angiogenesis in multiple ways. The ability of miR-126, one of the best-characterized miRNAs that regulates angiogenesis, carried by PLT-EXOs to influence angiogenesis via the regulation of the proliferation and migration of endothelial cells is unknown...
March 13, 2018: Current Vascular Pharmacology
Ya-Kun Li, Dong-Xia Ma, Zhi-Min Wang, Xiao-Fan Hu, Shang-Lin Li, Hong-Zhe Tian, Meng-Jun Wang, Yan-Wen Shu, Jun Yang
Renal fibrosis is recognized as the common route of all chronic kidney disease (CKD) progressing to end-stage renal disease (ESRD). Additionally, accumulating evidence suggests that epithelial-mesenchymal transition (EMT) plays a significant role in the process of renal fibrogenesis. Liraglutide is a long-acting glucagon-like peptide-1 (GLP-1) analog that has been widely used to treat type 2 diabetes. Recent studies have demonstrated that the GLP-1 analogs could also exert protective effects in cardiac fibrosis models...
March 9, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Hasan Alghetaa, Amira Mohammed, Muthanna Sultan, Philip Busbee, Angela Murphy, Saurabh Chatterjee, Mitzi Nagarkatti, Prakash Nagarkatti
Staphylococcal enterotoxin B (SEB) is a potent superantigen produced by Staphylococcus aureus that triggers a strong immune response, characterized by cytokine storm, multi-organ failure, and often death. When inhaled, SEB can cause acute lung injury (ALI) and respiratory failure. In this study, we investigated the effect of resveratrol (RES), a phytoallexin, on SEB-driven ALI and mortality in mice. We used a dual-exposure model of SEB in C3H/HeJ mice, which caused 100% mortality within the first 5 days of exposure, and treatment with RES resulted in 100% survival of these mice up to 10 days post-SEB exposure...
March 7, 2018: Journal of Cellular and Molecular Medicine
Nathan Cho, Shadi E Razipour, Megan L McCain
Cardiac fibroblasts and their activated derivatives, myofibroblasts, play a critical role in wound healing after myocardial injury and often contribute to long-term pathological outcomes, such as excessive fibrosis. Thus, defining the microenvironmental factors that regulate the phenotype of cardiac fibroblasts and myofibroblasts could lead to new therapeutic strategies. Both chemical and biomechanical cues have previously been shown to induce myofibroblast differentiation in many organs and species. For example, transforming growth factor beta 1, a cytokine secreted by neutrophils, and rigid extracellular matrix environments have both been shown to promote differentiation...
January 1, 2018: Experimental Biology and Medicine
Quan Jin, Chunping Qiao, Jianbin Li, Juan Li, Xiao Xiao
Growth and differentiation factor 11 (GDF11; BMP11) is a circulating cytokine in the transforming growth factor beta (TGF-β) superfamily. Treatment with recombinant GDF11 (rGDF11) protein has previously been shown to reverse skeletal muscle dysfunction in aged mice. However, the actions of GDF11 in skeletal muscle are still not fully understood. Because GDF11 activates the TGF-β-SMAD2/3 pathway, we hypothesized that GDF11 overexpression would inhibit skeletal muscle growth. To test this hypothesis, we generated recombinant adeno-associated virus serotype 9 (AAV9) vectors harboring the gene for either human GDF11 (AAV9-GDF11) or human IgG1 Fc-fused GDF11 propeptide (AAV9-GDF11Pro-Fc-1) to study the effects of GDF11 overexpression or blockade on skeletal muscle growth and function in vivo...
February 2, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Kevin J Morine, Xiaoying Qiao, Sam York, Peter S Natov, Vikram Paruchuri, Yali Zhang, Mark J Aronovitz, Richard H Karas, Navin K Kapur
Background -Heart failure is a growing cause of morbidity and mortality worldwide. Transforming growth factor beta (TGF-β1) promotes cardiac fibrosis, but also activates counter-regulatory pathways that serve to regulate TGF-β1 activity in heart failure. Bone morphogenetic protein 9 (BMP9) is a member of the TGFβ family of cytokines and signals via the downstream effector protein Smad1. Endoglin is a TGFβ co-receptor that promotes TGF-β1 signaling via Smad3 and binds BMP9 with high affinity. We hypothesized that BMP9 limits cardiac fibrosis by activating Smad1 and attenuating Smad3 and further that neutralizing endoglin activity promotes BMP9 activity...
February 27, 2018: Circulation
Mi-Yeon Jung, Jeong-Han Kang, Danielle M Hernandez, Xueqian Yin, Mahefatiana Andrianifahanana, Youli Wang, Anatilde Gonzalez-Guerrico, Andrew H Limper, Ruth Lupu, Edward B Leof
Evidence is provided that the fibroproliferative actions of TGF-β are dependent on a metabolic adaptation that sustains pathologic growth. Specifically, profibrotic TGF-β signaling is shown to require fatty acid synthase (FASN), an essential anabolic enzyme responsible for the de novo synthesis of fatty acids. With the use of pharmacologic and genetic approaches, we show that TGF-β-stimulated FASN expression is independent of Smad2/3 and is mediated via mammalian target of rapamycin complex 1. In the absence of FASN activity or protein, TGF-β-driven fibrogenic processes are reduced with no apparent toxicity...
February 16, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
J Lappalainen, N K J Oksala, D E Laaksonen, S Khanna, T Kokkola, K Kaarniranta, C K Sen, M Atalay
Impaired expression of heat shock proteins (HSPs) and increased oxidative stress may contribute to the pathophysiology of diabetes by disrupted tissue protection. Acute exercise induces oxidative stress, whereas exercise training up-regulates endogenous antioxidant defenses and HSP expression. Although diabetic nephropathy is a major contributor to diabetic morbidity, information regarding the effect of HSPs on kidney protection is limited. The present study evaluated the effects of 8-week exercise training on kidney HSP expression and markers of oxidative stress at rest and after acute exercise in rats with or without streptozotocin-induced diabetes...
February 23, 2018: Scandinavian Journal of Medicine & Science in Sports
Jos L van der Velden, Darcy E Wagner, Karolyn G Lahue, Sarah T Abdalla, Ying W Lam, Daniel J Weiss, Yvonne M W Janssen-Heininger
Epithelial cells have been suggested as potential drivers of lung fibrosis, although the epithelial-dependent pathways that promote fibrogenesis remain unknown. Extracellular matrix is increasingly recognized as an environment that can drive cellular responses in various pulmonary diseases. In this study, we demonstrate that transforming growth factor- beta (TGF-β1)-stimulated mouse tracheal basal (MTB) cells produce provisional matrix proteins in vitro, which initiate mesenchymal changes in subsequently freshly plated MTB cells via Rho kinase- and c-Jun-N-terminal kinase (JNK1)-dependent processes...
February 22, 2018: American Journal of Physiology. Lung Cellular and Molecular Physiology
G Bhaskaragoud, V Geetha, T Sharanappa, A S Mohan Kumar, C Hema Kumar, G Suresh Kumar
SCOPE: Diabetic nephropathy (DN) is a micro-vascular complication of chronic diabetes. Sterol regulatory element binding protein1 (SREBP1) participation in the development of DN is reported. Oryzanol Concentrate (OC) at 0.1 and 0.3% was tested for its antioxidant and hypolipidemic effects. The aim of the work was to study the involvement of OC in the amelioration of DN in STZ induced diabetic animal model. METHODS AND RESULTS: Animals were grouped into Starch, High fat and OC treated control/diabetic groups (SFC/SFD, HFC/HFD, OFC/OFD)...
February 22, 2018: Molecular Nutrition & Food Research
Priyanka Grover, Sritama Nath, Monica D Nye, Ru Zhou, Mohammad Ahmad, Pinku Mukherjee
Pancreatic Ductal Adenocarcinoma (PDA) has a mortality rate that nearly matches its incidence rate. Transforming Growth Factor Beta (TGF-β) is a cytokine with a dual role in tumor development switching from a tumor suppressor to a tumor promoter. There is limited knowledge of how TGF-β function switches during tumorigenesis. Mucin 1 (MUC1) is an aberrantly glycosylated, membrane-bound, glycoprotein that is overexpressed in >80% of PDA cases and is associated with poor prognosis. In PDA, MUC1 promotes tumor progression and metastasis via signaling through its cytoplasmic tail (MUC1-CT) and interacting with other oncogenic signaling molecules...
January 23, 2018: Oncotarget
Young Sun Hwang, Minseok Seo, Bo Ram Lee, Hong Jo Lee, Young Hyun Park, Sang Kyung Kim, Hyung Chul Lee, Hee Jung Choi, Joon Yoon, Heebal Kim, Jae Yong Han
The phylogenomics and comparative functional genomics of avian species were investigated in the Bird10K project because of the important evolutionary position of birds and their value as a research model. However, the systematic profiling of transcriptional changes prior to oviposition has not been investigated in avian species because of the practical difficulties in obtaining pre-oviposited eggs. In this study, a total of 137 pre-oviposited embryos were collected from hen ovaries and oviducts and subjected to RNA sequencing analyses...
February 21, 2018: Development
Hamed Haddad Kashani, Elahe Seyed Hosseini, Hossein Nikzad, Alireza Soleimani, Maryam Soleimani, Mohammad Reza Tamadon, Fariba Keneshlou, Zatollah Asemi
Objective: This study was carried out to determine the effects of vitamin D supplementation on signaling pathway of inflammation and oxidative stress in diabetic hemodialysis (HD) patients. Methods: This randomized double-blind placebo-controlled clinical trial was conducted among 60 diabetic HD patients. Subjects were randomly allocated into two groups to intake either vitamin D supplements at a dosage of 50,000 IU ( n = 30) or placebo ( n = 30) every 2 weeks for 12 weeks. Gene expression of inflammatory cytokines and biomarkers of oxidative stress were assessed in peripheral blood mononuclear cells (PBMCs) of diabetic HD patients with RT-PCR method...
2018: Frontiers in Pharmacology
Jianmei Wu, Yulin Ding, Jinling Wang, Fenglong Wang
Staphylococcus aureus is a common Gram-positive pathogen that causes bovine mastitis, a persistent infection of the bovine mammary gland. Bovine mammary epithelial cells (BMEC) are important parenchymal cells of the bovine mammary gland. To better understand the importance of BMEC and the roles of the TLR-NF-κBand TLR-AP-1 signaling pathways in the regulation of S. aureus-associated mastitis and mammary fibrosis, BMEC cultured in vitro were stimulated with different concentrations of heat-inactivated S. aureus to analyze the gene and protein expression and production of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), transforming growth factor beta 1 (TGF-β1), basic fibroblast growth factor (bFGF) as well as the protein expression of nuclear factor-kappa B (NF-κB) and activation protein-1 (AP-1) by means of quantitative polymerase chain reaction (qPCR) and western blotting, respectively...
February 13, 2018: Microbial Pathogenesis
Alessandro De Vita, Federica Recine, Laura Mercatali, Giacomo Miserocchi, Chiara Liverani, Chiara Spadazzi, Roberto Casadei, Alberto Bongiovanni, Federica Pieri, Nada Riva, Dino Amadori, Toni Ibrahim
Background: Myxofibrosarcoma (MFS), formerly considered as a myxoid variant of malignant fibrous histiocytoma, is the most common sarcoma of the extremities in adults and is characterized by a high frequency of local recurrence. The clinical behavior of MFS is unpredictable and the efficacy of chemotherapy is still not well documented. Furthermore, given the relatively recent recognition of MFS as a distinct pathologic entity its cellular and molecular biology has still not been extensively studied in patient-derived preclinical models...
December 2017: Therapeutic Advances in Medical Oncology
Chiara Giacomelli, Simona Daniele, Chiara Romei, Laura Tavanti, Tommaso Neri, Ilaria Piano, Alessandro Celi, Claudia Martini, Maria L Trincavelli
The epithelial-mesenchymal transition (EMT) is a complex process in which cell phenotype switches from the epithelial to mesenchymal one. The deregulations of this process have been related with the occurrence of different diseases such as lung cancer and fibrosis. In the last decade, several efforts have been devoted in understanding the mechanisms that trigger and sustain this transition process. Adenosine is a purinergic signaling molecule that has been involved in the onset and progression of chronic lung diseases and cancer through the A2B adenosine receptor subtype activation, too...
2018: Frontiers in Pharmacology
Daniil Nikitin, Dmitry Penzar, Andrew Garazha, Maxim Sorokin, Victor Tkachev, Nicolas Borisov, Alexander Poltorak, Vladimir Prassolov, Anton A Buzdin
Endogenous retroviruses and retrotransposons also termed retroelements (REs) are mobile genetic elements that were active until recently in human genome evolution. REs regulate gene expression by actively reshaping chromatin structure or by directly providing transcription factor binding sites (TFBSs). We aimed to identify molecular processes most deeply impacted by the REs in human cells at the level of TFBS regulation. By using ENCODE data, we identified ~2 million TFBS overlapping with putatively regulation-competent human REs located in 5-kb gene promoter neighborhood (~17% of all TFBS in promoter neighborhoods; ~9% of all RE-linked TFBS)...
2018: Frontiers in Immunology
Xiang Lin, Yongdong Dai, Wenzhi Xu, Libing Shi, Xiaoying Jin, Chao Li, Feng Zhou, Yibin Pan, Yinli Zhang, Xiaona Lin, Songying Zhang
Hypoxia plays a vital role in the progression of endometriosis. And integrin-mediated aberrant adhesion is also essential for establishment of endometriotic lesions. Here, we aim to determine the function of hypoxia in integrin-mediated adhesion of endometrial stromal cells (ESCs) in endometriosis. The expressions of adhesion molecule integrins (integrin-α5, integrin-αV, integrin-β3, and integrin-β5) were determined in 15 normal endometrium and 15 paired eutopic and ectopic endometrium by immunohistochemistry...
February 8, 2018: Endocrinology
Mercedes N Munkonda, Shareef Akbari, Chloe Landry, Suzy Sun, Fengxia Xiao, Maddison Turner, Chet E Holterman, Rania Nasrallah, Richard L Hébert, Christopher R J Kennedy, Dylan Burger
Tubulointerstitial fibrosis is a hallmark of advanced diabetic kidney disease that is linked to a decline in renal function, however the pathogenic mechanisms are poorly understood. Microparticles (MPs) are 100-1000 nm vesicles shed from injured cells that are implicated in intercellular signalling. Our lab recently observed the formation of MPs from podocytes and their release into urine of animal models of type 1 and 2 diabetes and in humans with type 1 diabetes. The purpose of the present study was to examine the role of podocyte MPs in tubular epithelial cell fibrotic responses...
2018: Journal of Extracellular Vesicles
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