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Wakako Tsuchida, Masahiro Iwata, Takayuki Akimoto, Shingo Matsuo, Yuji Asai, Shigeyuki Suzuki
It is generally recognized that synthetic glucocorticoids induce skeletal muscle weakness, and endogenous glucocorticoid levels increase in patients with muscle atrophy. It is reported that heat stress attenuates glucocorticoid-induced muscle atrophy; however, the mechanisms involved are unknown. Therefore, we examined the mechanisms underlying the effects of heat stress against glucocorticoid-induced muscle atrophy using C2C12 myotubes in vitro, focusing on expression of key molecules and signaling pathways involved in regulating protein synthesis and degradation...
September 20, 2016: Journal of Cellular Physiology
Sheila Patel, Elena Velkoska, Louise Burrell
OBJECTIVE: Left ventricular hypertrophy (LVH) is prevalent in chronic kidney disease (CKD) and a major cause of cardiovascular morbidity and mortality. Treatment of LVH in CKD is based on blood pressure control. The Kruppel like factor 15 (KLF15) is expressed in the heart and acts as a repressor of cardiac hypertrophy and fibrosis. The role of cardiac KLF15 in the development of LVH in rats with CKD secondary to subtotal nephrectomy (STNx) or the effects of ACE inhibition on KLF15 levels has not been addressed previously...
September 2016: Journal of Hypertension
Anastasia Mihailidou, Anthony Ashton
OBJECTIVE: Myocardial infarction (MI) continues to be a major burden of disease, despite rapid reperfusion interventions. Reperfusion of ischemic hearts (reperfusion injury) induces free radical generation, activation of early stress responses and apoptosis, which contributes to ventricular remodeling and dysfunction, which may lead to developing heart failure. Mineralocorticoid receptor (MR) antagonists have been shown clinically to reduce blood pressure, particularly in resistant hypertension, and substantially increase survival in heart failure...
September 2016: Journal of Hypertension
Deepesh Pandey, Daijiro Tori, Yohei Nomura, Dan Berkowitz, Lewis Romer
OBJECTIVE: Kruppel Like Factor 15 (KLF15) has recently been shown to be critical for activation of proinflammatory processes in vascular smooth muscle and atherogenesis. Although KLF15 is abundantly expressed in vascular endothelium there is a significant lack of knowledge regarding the role of KLF15 in the regulation of vascular endothelial function. Here we tested the hypothesis that KLF15 is a critical regulator of Arg2 transcription in hypoxia exposed human pulmonary microvascular endothelial cells (HPMEC) and that it plays critical role in pathogenesis of pulmonary hypertension (PHTN)...
September 2016: Journal of Hypertension
Ke Wang, Yu Ren, Yang Liu, Jian Zhang, Jian-Jun He
MiRNAs have been shown to be involved in breast cancer growth and progression. MiR-4262 is a potential tumor promoter in human cancers. In this study, we first investigated the role of miR-4262 in the proliferation and invasion of human breast cancer cells. Our results showed that, compared with the adjacent tissues and MCF-10A normal breast epithelial cells, miR-4262 was markedly increased in the breast cancer tissues and 5 cell lines, including MDA-MB-231, MDA-MB-468, MDA-MB-435, SKBR3 and MCF-7. Then, the miR-4262 mimic or oligo anta-miR-4262 was transfected into MDA-MB-231 and MCF-7 breast cancer cell lines...
September 13, 2016: Oncology Research
Yoshinori Takeuchi, Naoya Yahagi, Yuichi Aita, Yuki Murayama, Yoshikazu Sawada, Xiaoying Piao, Naoki Toya, Yukari Oya, Akito Shikama, Ayako Takarada, Yukari Masuda, Makiko Nishi, Midori Kubota, Yoshihiko Izumida, Takashi Yamamoto, Motohiro Sekiya, Takashi Matsuzaka, Yoshimi Nakagawa, Osamu Urayama, Yasushi Kawakami, Yoko Iizuka, Takanari Gotoda, Keiji Itaka, Kazunori Kataoka, Ryozo Nagai, Takashi Kadowaki, Nobuhiro Yamada, Yuan Lu, Mukesh K Jain, Hitoshi Shimano
Hepatic lipogenesis is nutritionally regulated (i.e., downregulated during fasting and upregulated during the postprandial state) as an adaptation to the nutritional environment. While alterations in the expression level of the transcription factor SREBP-1c are known to be critical for nutritionally regulated lipogenesis, upstream mechanisms governing Srebf1 expression remain unclear. Here, we show that the fasting-induced transcription factor KLF15, a key regulator of gluconeogenesis, forms a complex with LXR/RXR, specifically on the Srebf1 promoter...
August 30, 2016: Cell Reports
Jianbo Wang, Joana Galvao, Krista M Beach, Weijia Luo, Raul A Urrutia, Jeffrey L Goldberg, Deborah C Otteson
Regenerative medicine holds great promise for the treatment of degenerative retinal disorders. Krüppel-like factors (KLFs) are transcription factors that have recently emerged as key tools in regenerative medicine because some of them can function as epigenetic reprogrammers in stem cell biology. Here, we show that KLF16, one of the least understood members of this family, is a POU4F2 independent transcription factor in retinal ganglion cells (RGCs) as early as embryonic day 15. When overexpressed, KLF16 inhibits RGC neurite outgrowth and enhances RGC growth cone collapse in response to exogenous ephrinA5 ligands...
August 26, 2016: Journal of Biological Chemistry
Anning Li, Lijuan Wu, Xiaoyu Wang, Yaping Xin, Linsen Zan
Fatty acid binding protein 3 (FABP3) is a member of the FABP family which bind fatty acids and have an important role in fatty acid metabolism. A large number of studies have shown that the genetic polymorphisms of FABP3 are positively correlated with intramuscular fat (IMF) content in domestic animals, however, the function and transcriptional characteristics of FABP3 in cattle remain unclear. Real-time PCR analysis revealed that bovine FABP3 was highly expressed in cardiac tissue. The 5'-regulatory region of bovine FABP3 was cloned and its transcription initiation sites were identified...
September 2016: Molecular Biology Reports
Xiaoming Hu, Yuanfei Zhou, Yang Yang, Jie Peng, Tongxing Song, Tao Xu, Hongkui Wei, Siwen Jiang, Jian Peng
Adipose tissue is a key determinant of whole-body metabolism and energy homeostasis. Unravelling the transcriptional regulatory process during adipogenesis is therefore highly relevant from a biomedical perspective. In these studies, zinc finger protein B-cell lymphoma 6 (Bcl6) was demonstrated to have a role in early adipogenesis of mesenchymal stem cells. Bcl6 is enriched in preadipose versus non-preadipose fibroblasts and shows upregulated expression in the early stage of adipogenesis. Gain- and loss-of-function studies revealed that Bcl6 acts as a key regulator of adipose commitment and differentiation both in vitro and ex vivo RNAi-mediated knockdown of Bcl6 in C3H10T1/2 cells greatly inhibited adipogenic potential, whereas Bcl6 overexpression enhanced adipogenic differentiation...
June 2016: Open Biology
Cuizhe Wang, Xiaodan Ha, Wei Li, Peng Xu, Yajuan Gu, Tingting Wang, Yan Wang, Jianxin Xie, Jun Zhang
In this paper, the researchers collected visceral adipose tissue from the Uygur population, which were divided into two groups: the normal control group (NC, n = 50, 18.0 kg/m(2) ≤ BMI ≤ 23.9 kg/m(2)) and the obese group (OB, n = 45, BMI ≥ 28 kg/m(2)), and then use real-time PCR to detect the mRNA expression level of key genes involved in inflammation signaling pathway. The findings suggest that, in obese status, the lower expression level of A2bAR, KLF4, and KLF15 of visceral adipose tissue may correlate with obese-dyslipidemia induced inflammation in Uygur population...
2016: Mediators of Inflammation
Dalia Ali, Rimi Hamam, Musaed Alfayez, Moustapha Kassem, Abdullah Aldahmash, Nehad M Alajez
UNLABELLED: : The epigenetic mechanisms promoting lineage-specific commitment of human skeletal (mesenchymal or stromal) stem cells (hMSCs) into adipocytes or osteoblasts are still not fully understood. Herein, we performed an epigenetic library functional screen and identified several novel compounds, including abexinostat, which promoted adipocytic and osteoblastic differentiation of hMSCs. Using gene expression microarrays, chromatin immunoprecipitation for H3K9Ac combined with high-throughput DNA sequencing (ChIP-seq), and bioinformatics, we identified several key genes involved in regulating stem cell proliferation and differentiation that were targeted by abexinostat...
August 2016: Stem Cells Translational Medicine
Z Z Yin, X Y Dong, D J Dong, Y Z Ma
1. Single Nucleotide Polymorphisms (SNPs) in the exons of the MYF5 (Myogenic factor 5) and KLF15 (Kruppel-like factor 15) genes were identified and analysed by using DNA sequencing methods in 60 female domestic pigeons (Columba livia). 2. Five SNPs (T5067A, C5084T, C5101T, T5127A and C5154G) were detected in exon 3 of MYF5 and 6 SNPs (C1398T, C1464T, G1542A, C1929T, G1965A and A2355G) were found in exon 2 of KLF15, respectively. The analysis revealed 3 genotypes, in which the AA genotype was dominant and the A allele showed a dominant advantage...
May 16, 2016: British Poultry Science
Melvin Anyasi Ambele, Carla Dessels, Chrisna Durandt, Michael Sean Pepper
We have undertaken an in-depth transcriptome analysis of adipogenesis in human adipose-derived stromal cells (ASCs) induced to differentiate into adipocytes in vitro. Gene expression was assessed on days 1, 7, 14 and 21 post-induction and genes differentially expressed numbered 128, 218, 253 and 240 respectively. Up-regulated genes were associated with blood vessel development, leukocyte migration, as well as tumor growth, invasion and metastasis. They also shared common pathways with certain obesity-related pathophysiological conditions...
May 2016: Stem Cell Research
Haipeng Sun, Kristine C Olson, Chen Gao, Domenick A Prosdocimo, Meiyi Zhou, Zhihua Wang, Darwin Jeyaraj, Ji-Youn Youn, Shuxun Ren, Yunxia Liu, Christoph D Rau, Svati Shah, Olga Ilkayeva, Wen-Jun Gui, Noelle S William, R Max Wynn, Christopher B Newgard, Hua Cai, Xinshu Xiao, David T Chuang, Paul Christian Schulze, Christopher Lynch, Mukesh K Jain, Yibin Wang
BACKGROUND: Although metabolic reprogramming is critical in the pathogenesis of heart failure, studies to date have focused principally on fatty acid and glucose metabolism. Contribution of amino acid metabolic regulation in the disease remains understudied. METHODS AND RESULTS: Transcriptomic and metabolomic analyses were performed in mouse failing heart induced by pressure overload. Suppression of branched-chain amino acid (BCAA) catabolic gene expression along with concomitant tissue accumulation of branched-chain α-keto acids was identified as a significant signature of metabolic reprogramming in mouse failing hearts and validated to be shared in human cardiomyopathy hearts...
May 24, 2016: Circulation
Yajun Yang, Yanjie Su, Dongtao Wang, Yahui Chen, Yuyu Liu, Shiying Luo, Tie Wu, Liao Cui
Decreased bone formation is responsible for the pathogenesis of glucocorticoid- (GC-) induced osteoporosis (GIO), while the mechanism remains to be elucidated. The aim was to investigate how natural antioxidant tanshinol attenuates oxidative stress and rescues impaired bone formation elicited by GC in Sprague-Dawley rats and in C2C12 cells and/or MC3T3-E1 cells. The results showed that tanshinol prevented bone loss and decreased biomechanical characteristics and suppressed reduction of biomarkers related to osteogenesis in GIO rats...
2016: Oxidative Medicine and Cellular Longevity
Zhi-Dong Zhao, Lin-Sen Zan, An-Ning Li, Gong Cheng, Shi-Jun Li, Ya-Ran Zhang, Xiao-Yu Wang, Ying-Ying Zhang
The nutritional value and eating qualities of beef are enhanced when the unsaturated fatty acid content of fat is increased. Long-chain acyl-CoA synthetase 1 (ACSL1) plays key roles in fatty acid transport and degradation, as well as lipid synthesis. It has been identified as a plausible functional and positional candidate gene for manipulations of fatty acid composition in bovine skeletal muscle. In the present study, we determined that bovine ACSL1 was highly expressed in subcutaneous adipose tissue and longissimus thoracis...
2016: Scientific Reports
Diana Monsivais, Caterina Clementi, Jia Peng, Mary M Titus, James P Barrish, Chad J Creighton, John P Lydon, Francesco J DeMayo, Martin M Matzuk
The window of implantation is defined by the inhibition of uterine epithelial proliferation, structural epithelial cell remodeling, and attenuated estrogen (E2) response. These changes occur via paracrine signaling between the uterine epithelium and stroma. Because implantation defects are a major cause of infertility in women, identifying these signaling pathways will improve infertility interventions. Bone morphogenetic proteins (BMPs) are TGF-β family members that regulate the postimplantation and midgestation stages of pregnancy...
January 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
Da Som Lee, Hyeonjin Choi, Baek Soo Han, Won Kon Kim, Sang Chul Lee, Kyoung-Jin Oh, Kwang-Hee Bae
Abnormal adipocyte differentiation is implicated in the development of metabolic disorders such as obesity and type II diabetes. Thus, an in-depth understanding of the molecular mechanisms associated with adipocyte differentiation is the first step in overcoming obesity and its related metabolic diseases. Here, we examined the role of c-Jun as a transcription factor in adipocyte differentiation. c-Jun overexpression in murine 3T3-L1 preadipocytes significantly inhibited adipocyte differentiation. In addition, the expression level of KLF15, an upstream effector of the key adipogenic factors C/EBPα and PPARγ, was decreased upon the ectopic expression of c-Jun...
January 15, 2016: Biochemical and Biophysical Research Communications
Lilei Zhang, Domenick A Prosdocimo, Xiaodong Bai, Chen Fu, Rongli Zhang, Frank Campbell, Xudong Liao, Jeff Coller, Mukesh K Jain
Circadian rhythms offer temporal control of anticipatory physiologic adaptations in animals. In the mammalian cardiovascular system, the importance of these rhythms is underscored by increased cardiovascular disease in shift workers, findings recapitulated in experimental animal models. However, a nodal regulator that allows integration of central and peripheral information and coordinates cardiac rhythmic output has been elusive. Here, we show that kruppel-like factor 15 (KLF15) governs a biphasic transcriptomic oscillation in the heart with a maximum ATP production phase and a remodeling and repair phase corresponding to the active and resting phase of a rodent...
December 22, 2015: Cell Reports
Botao Zhan, Zhipeng Hu, Jiajun Chen, Rui Zhu, Hua Zhao, Junbo Yang, Zengwang Zhang, Ronghua Nie
Background KLF15 (Krüppel-like factor 15) was reported to be involved in a lot of cardiovascular diseases. Little is known about its role in initiation and development of aortic dissection (AD). Methods Samples of the human aorta were collected during AD surgery and aortic valve replacement. Lentivirus was used for in vitro and in vivo KLF15 overexpression in BAPN (β-aminopropionitrile)-induced rat AD models. The survival times were recorded and compared between the two groups. Autopsy was used for confirming aorta rupture in rat models...
November 24, 2015: Thoracic and Cardiovascular Surgeon
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