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Toshiaki Takahashi, Julia Zimmer, Florian Friedmacher, Prem Puri
BACKGROUND/PURPOSE: Pulmonary hypoplasia (PH), characterized by incomplete alveolar development, remains a major therapeutic challenge associated with congenital diaphragmatic hernia (CDH). Follistatin-like 1 (Fstl1) is a crucial regulator of alveolar formation and maturation, which is strongly expressed in distal airway epithelium. Fstl1-deficient mice exhibit reduced airspaces, impaired alveolar epithelial cell differentiation, and insufficient production of surfactant proteins similar to PH in human CDH...
January 28, 2017: Journal of Pediatric Surgery
Kathryn Tully Oelsner, Yan Guo, Sophie Bao-Chieu To, Amy L Non, Shari L Barkin
BACKGROUND: The study of epigenetic processes and mechanisms present a dynamic approach to assess complex individual variation in obesity susceptibility. However, few studies have examined epigenetic patterns in preschool-age children at-risk for obesity despite the relevance of this developmental stage to trajectories of weight gain. We hypothesized that salivary DNA methylation patterns of key obesogenic genes in Hispanic children would 1) correlate with maternal BMI and 2) allow for identification of pathways associated with children at-risk for obesity...
January 9, 2017: BMC Genomics
Kathryn L Pothoven, James E Norton, Lydia A Suh, Roderick G Carter, Kathleen E Harris, Assel Biyasheva, Kevin Welch, Stephanie Shintani-Smith, David B Conley, Mark C Liu, Atsushi Kato, Pedro C Avila, Qutayba Hamid, Leslie C Grammer, Anju T Peters, Robert C Kern, Bruce K Tan, Robert P Schleimer
BACKGROUND: We have previously shown that oncostatin M (OSM) levels are increased in nasal polyps (NPs) of patients with chronic rhinosinusitis (CRS), as well as in bronchoalveolar lavage fluid, after segmental allergen challenge in allergic asthmatic patients. We also showed in vitro that physiologic levels of OSM impair barrier function in differentiated airway epithelium. OBJECTIVE: We sought to determine which hematopoietic or resident cell type or types were the source of the OSM expressed in patients with mucosal airways disease...
December 18, 2016: Journal of Allergy and Clinical Immunology
Shifeng Su, Amanda B Parris, Gail Grossman, James L Mohler, Zengjun Wang, Elizabeth M Wilson
BACKGROUND: High affinity androgen binding to the androgen receptor (AR) activates genes required for male sex differentiation and promotes the development and progression of prostate cancer. Human AR transcriptional activity involves interactions with coregulatory proteins that include primate-specific melanoma antigen-A11 (MAGE-A11), a coactivator that increases AR transcriptional activity during prostate cancer progression to castration-resistant/recurrent prostate cancer (CRPC). METHODS: Microarray analysis and quantitative RT-PCR were performed to identify androgen-regulated MAGE-A11-dependent genes in LAPC-4 prostate cancer cells after lentivirus shRNA knockdown of MAGE-A11...
December 14, 2016: Prostate
Kai-Yuan Cheng, Yi Liu, Ying-Guang Han, Jing-Kun Li, Jia-Lin Jia, Bin Chen, Zhi-Xiao Yao, Lin Nie, Lei Cheng
Follistain-like protein 1 (FSTL1), has been recently demonstrated to be involved in the embryo development of nervous system and glioblastoma. However, the role of FSTL1 in neuroinflammation remains unexplored. In this study, the expression of FSTL1 in astrocytes was verified and its role was studied in neuroinflammation induced by in vivo intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) or LPS treatment to astrocytes in vitro. FSTL1 was significantly induced after ICV LPS injection or LPS treatment...
December 2, 2016: Journal of Molecular Histology
Hong Wang, Senyong Wu, Shiping Huang, Shaolin Yin, Guilong Zou, Kuan'en Huang, Zhe Zhang, Anzhou Tang, Wensheng Wen
Follistatin-like protein 1 (FSTL1) is a newly characterized protein that can regulate the immune response in various ways. Dendritic cells (DCs) are central to immune regulation. In this study, we explored the impact of FSTL1 on DC activity in nasopharyngeal carcinoma (NPC) patients. The surface expression of CD40, CD86, and HLA-DR on DCs was analyzed and showed significantly elevated expression levels, indicating DC maturity. After FSTL1 was added to DCs collected from NPC patients (n = 50), controls (n = 47), and healthy donors (n = 10), interferon γ secretion and T-cell receptor expression in cytotoxic T lymphocytes were also investigated...
December 2016: Cell Biochemistry and Function
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...
August 1, 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...
May 26, 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
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