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Junxia Guo, Wanqian Liang, Jianhua Li, Jingning Long
Activation of inflammation by oxidized low-density lipoprotein (oxLDL) has been implicated in the development of atherosclerosis. Follistatin-like protein 1 (FSTL1) play a central role in the inflammation process and modulate cardiovascular disorders. However, little is known about the effects of FSTL1 on the inflammation induced by oxLDL. The aim of this study was to evaluate the anti-inflammatory effect of FSTL1 and investigate potential mechanisms in cultured endothelial cells. A model of oxLDL-induced injury in human coronary artery endothelial cells (HCAECs) was established to evaluate the protective role of FSTL1...
September 30, 2016: Biochemical and Biophysical Research Communications
Yue Xi, Da-Wei Gong, Zhenjun Tian
Exercise training has been reported to ameliorate heart dysfunction in both humans and animals after myocardial infarction (MI), but the underlying mechanisms are poorly understood. Follistatin-like1 (FSTL1) is a cardioprotective factor against ischemic injury and is induced in cardiomyocytes and skeletal muscle in ischemic and hypoxic conditions. To test the hypothesis that FSTL1 may be a molecular link between exercise and improved heart function post MI, we subjected MI-rats, induced by left coronary artery ligation, to two modes of exercise: intermittent aerobic exercise (IAE) or mechanical vibration training (MVT), for four weeks and examined the relevance of FSTL1 to exercise-mediated cardiac effects...
2016: Scientific Reports
Kihoon Cha, Yi Li, Gwan-Su Yi
BACKGROUND: Tyrosine kinase inhibitor (TKI)-based therapy is a recommended treatment for patients with chronic myeloid leukemia (CML). However, a considerable group of CML patients do not respond well to the TKI therapy. Challenging to overcome this problem, we tried to discover molecular signatures in gene expression profiles to discriminate the responders and non-responders of TKI therapy. METHODS: We collected three microarray datasets of CML patients having total 73 responders and 38 non-responders...
2016: BMC Medical Genomics
Dong-Liang Shi, Gui-Rong Shi, Jing Xie, Xu-Zhao Du, Hao Yang
Fibroblast-like synoviocytes (FLS) with aberrant expression of microRNA (miRNA) are critical pathogenic regulators in rheumatoid arthritis (RA). Previous studies have found that overexpression or silencing of miRNA can contribute to the development of miRNA-based therapeutics in arthritis models. In this study, we explored the effects of miR-27a on cell migration and invasion in cultured FLS from RA patients. We found that miR-27a was markedly downregulated in the serum, synovial tissue, and FLS of RA patients...
August 31, 2016: Molecules and Cells
M Q Zhang, H Chen, C L Zhai, J F Tu, Y Shen, L X Pang, Q R Xu
OBJECTIVE: To investigate the role of follistatin-like protein 1 (FSTL1) on bone marrow mesenchymal stem cells (BM-MSCs)-mediated cardioprotection during myocardial ischemia/reperfusion injury. METHODS: Rat bone marrow mesenchymal stem cells were isolated by whole bone marrow adherence method in vitro. A total of 60 Wistar rats were randomly divided into 4 groups: control group, ischemic /reperfusion injury (IRI) group, ischemia/reperfusion injury group treated with natural BM-MSCs (IRI+ MSC group), ischemia/reperfusion injury group treated with BM-MSCs which did not contain FSTL1 (IRI+ MSC FSTL1 siRNA group)...
July 5, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Komei Tanaka, María Valero-Muñoz, Richard M Wilson, Eric E Essick, Conor T Fowler, Kazuto Nakamura, Maurice van den Hoff, Noriyuki Ouchi, Flora Sam
OBJECTIVE: We sought to determine whether Fstl1 plays a role in the regulation of cardiac hypertrophy in HFpEF. BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF), accounts for ~50% of all clinical presentations of HF and its prevalence is expected to increase. However, there are no evidence-based therapies for HFpEF; thus, HFpEF represents a major unmet need. Although hypertension is the single most important risk factor for HFpEF, with a prevalence of 60-89% from clinical trials and human HF registries, blood pressure therapy alone is insufficient to prevent and treat HFpEF...
June 2016: JACC. Basic to Translational Science
Luc Rochette, Catherine Vergely
The mechanisms of aging and senescence include various endogenous and exogenous factors. Among cardiovascular diseases, heart failure is a typical age-related disease. New strategies to restore cardiomyocyte cells have been reported: endogenous substances that can regenerate the heart's cardiomyocytes have been described: follistatin like 1 (FSTL1), growth-differentiation factor 11 (GDF11) and insulin-like growth factor 1 (IGF-I). Manipulation of the different anti and pro- pathways is essential to discover new approaches to regenerative therapies...
October 2016: Experimental Gerontology
Jun Feng Liu, Yi Shuai Li, Paul A Drew, Chao Zhang
This study examined the in-vivo effect of the NSAID celecoxib on DNA methylation in the promoter region of the tumor-suppressor genes cadherin 13, tissue factor pathway inhibitor 12, and follistatin-like protein 1, and on apoptosis, in esophageal squamous cell carcinoma (ESCC). Forty-five patients who underwent an esophagectomy for ESCC were allocated to either a treatment group (n=22) or a control group (n=23). Patients in the treatment group were administered 800 mg/day of celecoxib for 14 days before surgery...
October 2016: Anti-cancer Drugs
Xiaohe Li, Yinshan Fang, Xue Li, Jiurong Liang, Dianhua Jiang, Yan Geng, Wen Ning
Follistatin-like 1 (FSTL1) is a secreted bone morphogenetic protein (BMP) antagonist, and it plays a crucial role in normal lung development. Deletion of Fstl1 leads to postnatal death in mice due to respiratory failure. To further explore the role of FSTL1 in mouse lung development, we created a transgene SFTPC-Fstl1 allele mouse displaying significant epithelial overexpression of Fstl1 in all stages of lung development. However, epithelial overexpression of Fstl1 did not alter lung morphogenesis, epithelial differentiation and lung function...
2016: PloS One
Sonomi Maruyama, Kazuto Nakamura, Kyriakos N Papanicolaou, Soichi Sano, Ippei Shimizu, Yasuhide Asaumi, Maurice J van den Hoff, Noriyuki Ouchi, Fabio A Recchia, Kenneth Walsh
Follistatin-like 1 (Fstl1) is a secreted protein that is acutely induced in heart following myocardial infarction (MI). In this study, we investigated cell type-specific regulation of Fstl1 and its function in a murine model of MI Fstl1 was robustly expressed in fibroblasts and myofibroblasts in the infarcted area compared to cardiac myocytes. The conditional ablation of Fstl1 in S100a4-expressing fibroblast lineage cells (Fstl1-cfKO mice) led to a reduction in injury-induced Fstl1 expression and increased mortality due to cardiac rupture during the acute phase...
2016: EMBO Molecular Medicine
Hyun-Ju Kim, Woo Youl Kang, Sook Jin Seong, Shin-Yoon Kim, Mi-Sun Lim, Young-Ran Yoon
Follistatin-like 1 (FSTL1) functions as a pivotal modulator of inflammation and is implicated in many inflammatory diseases such as rheumatoid arthritis. Here, we report that FSTL1 is strongly upregulated and secreted during osteoclast differentiation of bone marrow-derived macrophages (BMMs) and that FSTL1 positively regulates osteoclast formation induced by RANKL and M-CSF. The overexpression of FSTL1 or treatment with recombinant FSTL1 (rFSTL1) in BMMs enhances the formation of multinuclear osteoclasts and the induction of c-Fos and NFATc1, transcription factors important for osteoclastogenesis...
September 2016: Cellular Signalling
Yan Liu, Xue Han, Yongwei Yu, Yibo Ding, Chong Ni, Wenbin Liu, Xiaomei Hou, Zixiong Li, Jianguo Hou, Dan Shen, Jianhua Yin, Hongwei Zhang, Timothy C Thompson, Xiaojie Tan, Guangwen Cao
Few single nucleotide polymorphisms (SNPs) associated with the risk of renal cell carcinoma (RCC) have been identified, yet genetic predisposition contributes significantly to this malignancy. We previously showed that follistatin-like 1 (FSTL1) was significantly down-regulated in clear cell RCC (ccRCC), in particular metastatic ccRCC. In the present study, we systemically investigated the associations of the 6 SNPs within FSTL1-coding genomic region with RCC risk and postoperative prognosis. Age- and gender-matched case-control study (417 vs 855) indicated that rs1259293 variant genotype CC was significantly associated with an increased risk of RCC, with an odds ratio of 2...
2016: Scientific Reports
Satoko Hayakawa, Koji Ohashi, Rei Shibata, Ryotaro Takahashi, Naoya Otaka, Hayato Ogawa, Masanori Ito, Noriyoshi Kanemura, Mizuho Hiramatsu-Ito, Nobuo Ikeda, Toyoaki Murohara, Noriyuki Ouchi
OBJECTIVES: Follistatin-like 1 (Fstl1) is a circulating glycoprotein that plays a crucial role in cardiovascular diseases and inflammation-related disorders. We have shown that Fstl1 acts as an anti-inflammatory factor that protects against ischemic heart disease and chronic kidney disease. Here we examined whether plasma level of Fstl1 associates with markers of inflammation and oxidative stress in apparently healthy Japanese men. METHODS AND RESULTS: Plasma Fstl1 levels were measured by enzyme-linked immunosorbent assay...
2016: PloS One
Xiaoying Zhou, Xue Xiao, Tingting Huang, Chunping Du, Shumin Wang, Yingxi Mo, Ning Ma, Mariko Murata, Bo Li, Wensheng Wen, Guangwu Huang, Xianjie Zeng, Zhe Zhang
Follistatin like-1 (FSTL1) is a secreted glycoprotein involved in a series of physiological and pathological processes. However, its contribution to the development of cancer, especially the pathogenesis of nasopharyngeal carcinoma (NPC), remains to be elucidated. We aimed to investigate the dysregulation of FSTL1 and its possible function in NPC. FSTL1 was frequently downregulated in NPC cell lines and primary tumor biopsies by promoter hypermethylation. Ectopic expression of FSTL1 significantly suppressed the colony formation, proliferation, migration and invasion ability of NPC cells and induced cell apoptosis...
March 29, 2016: Oncotarget
Bing-Lu Li, Jin-Dou An, Song Feng, Wei Ge
OBJECTIVE: To investigate the change in the serum level of follistatin-like protein 1 (FSTL1) in children with chronic heart failure and its correlation with left ventricular remodeling. METHODS: A total of 45 children with chronic heart failure (CHF) between May 2014 and May 2015 were selected as the CHF group, among whom 21 had endocardial fibroelastosis (EFE) and 24 had dilated cardiomyopathy (DCM); another 30 healthy children were selected as the control group...
February 2016: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
Per Holmfeldt, Miguel Ganuza, Himangi Marathe, Bing He, Trent Hall, Guolian Kang, Joseph Moen, Jennifer Pardieck, Angelica C Saulsberry, Alba Cico, Ludovic Gaut, Daniel McGoldrick, David Finkelstein, Kai Tan, Shannon McKinney-Freeman
Understanding the molecular regulation of hematopoietic stem and progenitor cell (HSPC) engraftment is paramount to improving transplant outcomes. To discover novel regulators of HSPC repopulation, we transplanted >1,300 mice with shRNA-transduced HSPCs within 24 h of isolation and transduction to focus on detecting genes regulating repopulation. We identified 17 regulators of HSPC repopulation: Arhgef5, Armcx1, Cadps2, Crispld1, Emcn, Foxa3, Fstl1, Glis2, Gprasp2, Gpr56, Myct1, Nbea, P2ry14, Smarca2, Sox4, Stat4, and Zfp251...
March 7, 2016: Journal of Experimental Medicine
Noelle Murphy, Katherine U Gaynor, Simon C Rowan, Sinead M Walsh, Aurelie Fabre, John Boylan, Michael P Keane, Paul McLoughlin
Idiopathic pulmonary fibrosis is a chronic, progressive fibrotic disease with a poor prognosis. The balance between transforming growth factor β1 and bone morphogenetic protein (BMP) signaling plays an important role in tissue homeostasis, and alterations can result in pulmonary fibrosis. We hypothesized that multiple BMP accessory proteins may be responsible for maintaining this balance in the lung. Using the bleomycin mouse model for fibrosis, we examined an array of BMP accessory proteins for changes in mRNA expression...
March 2016: American Journal of Pathology
Kieun Bae, Kyoung Eun Park, Jihye Han, Jongkwang Kim, Kyungtae Kim, Kyong-Ah Yoon
Follistatin-like 1 (FSTL1) was identified as a novel pro-inflammatory protein showing high-level expression in rheumatoid arthritis. The protective effect of FSTL1 via the inhibition of apoptosis was reported in myocardial injury. However, the functional mechanism of FSTL1 in cancer is poorly characterized, and its proliferative effects are ambiguous. Here, we examined the effects of FSTL1 on cellular proliferation and cell cycle checkpoints in lung cancer cells. FSTL1 inhibition induced the cellular portion of G2/M phase in human lung cancer cells via the accumulation of regulators of the transition through the G2/M phase, including the cyclin-dependent kinase 1 (Cdk1)-cyclin B1 complex...
April 5, 2016: Oncotarget
Weiqian Chen, Jun Xia, Ping Hu, Fei Zhou, Yueqiu Chen, Jianping Wu, Wei Lei, Zhenya Shen
Cardiac cell apoptosis provoked by excessive sodium nitroprusside (SNP) toxicity, a potent vasodilator, limited its clinical application. Effective means for protection against SNP-induced cardiotoxicity would be highly needed. This study investigated the effects of Follistatin-like 1 (FSTL1) on the injury induced by SNP in rat cardiomyoblast H9c2 cells. First, expression of FSTL is attenuated following SNP treatment. SNP challenge significantly increases cardiac cell death, which is attenuated by FSTL1 pretreatment...
January 15, 2016: Biochemical and Biophysical Research Communications
Ann-Kristin Alteköester, Richard P Harvey
Improving the limited ability of the heart to regenerate after infarction is crucial. Researchers now demonstrate that delivery of follistatin-like 1 (FSTL1) into injured hearts via collagen patches stimulates cardiomyocyte proliferation and cardiac functional recovery. These findings highlight the epicardium as a source of novel regenerative factors and biomimetic nanomaterials in cardiac translational medicine.
December 2015: Trends in Molecular Medicine
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