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https://www.readbyqxmd.com/read/29901095/loss-of-klf15-accelerates-chronic-podocyte-injury
#1
Seung Seok Han, Mi-Yeon Yu, Kyung Don Yoo, Jung Pyo Lee, Dong Ki Kim, Yon Su Kim, Seung Hee Yang
Krüppel‑like factor 15 (KLF15), also known as kidney‑enriched transcription factor, is known to participate in podocyte differentiation. However, the role of KLF15 in chronic podocyte injury remains incompletely understood, particularly in proteinuric disease models. In the present study, the 5/6 nephrectomy mouse model was used to induce chronic podocyte injury. Human primary podocytes were isolated by flow cytometry and cultured to emulate the injury process in an in vitro system. Biopsied kidney tissue samples were obtained from patients with primary membranous nephropathy or diabetic nephropathy in order to analyze the relationship between glomerular KLF15 expression and subsequent outcomes...
June 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29735415/interventions-targeting-glucocorticoid-kr%C3%A3-ppel-like-factor-15-branched-chain-amino-acid-signaling-improve-disease-phenotypes-in-spinal-muscular-atrophy-mice
#2
Lisa M Walter, Marc-Olivier Deguise, Katharina E Meijboom, Corinne A Betts, Nina Ahlskog, Tirsa L E van Westering, Gareth Hazell, Emily McFall, Anna Kordala, Suzan M Hammond, Frank Abendroth, Lyndsay M Murray, Hannah K Shorrock, Domenick A Prosdocimo, Saptarsi M Haldar, Mukesh K Jain, Thomas H Gillingwater, Peter Claus, Rashmi Kothary, Matthew J A Wood, Melissa Bowerman
The circadian glucocorticoid-Krüppel-like factor 15-branched-chain amino acid (GC-KLF15-BCAA) signaling pathway is a key regulatory axis in muscle, whose imbalance has wide-reaching effects on metabolic homeostasis. Spinal muscular atrophy (SMA) is a neuromuscular disorder also characterized by intrinsic muscle pathologies, metabolic abnormalities and disrupted sleep patterns, which can influence or be influenced by circadian regulatory networks that control behavioral and metabolic rhythms. We therefore set out to investigate the contribution of the GC-KLF15-BCAA pathway in SMA pathophysiology of Taiwanese Smn-/- ;SMN2 and Smn2B/- mouse models...
May 4, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29731773/romidepsin-promotes-osteogenic-and-adipocytic-differentiation-of-human-mesenchymal-stem-cells-through-inhibition-of-histondeacetylase-activity
#3
Dalia Ali, Elna P Chalisserry, Muthurangan Manikandan, Rimi Hamam, Musaad Alfayez, Moustapha Kassem, Abdullah Aldahmash, Nehad M Alajez
Bone marrow mesenchymal stem cells (BMSCs) are adult multipotent stem cells that can differentiate into mesodermal lineage cells, including adipocytes and osteoblasts. However, the epigenetic mechanisms governing the lineage-specific commitment of BMSCs into adipocytes or osteoblasts are under investigation. Herein, we investigated the epigenetic effect of romidepsin, a small molecule dual inhibitor targeting HDAC1 and HDAC2 identified through an epigenetic library functional screen. BMSCs exposed to romidepsin (5 nM) exhibited enhanced adipocytic and osteoblastic differentiation...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29702551/kruppel-like-factor-15-is-critical-for-the-development-of-left-ventricular-hypertrophy
#4
REVIEW
Sheila K Patel, Jay Ramchand, Vincenzo Crocitti, Louise M Burrell
Left ventricular hypertrophy (LVH) is an independent risk factor for adverse cardiovascular events and is often present in patients with hypertension. Treatment to reduce blood pressure and regress LVH is key to improving health outcomes, but currently available drugs have only modest cardioprotective effects. Improved understanding of the molecular mechanisms involved in the development of LVH may lead to new therapeutic targets in the future. There is now compelling evidence that the transcription factor Kruppel-like factor 15 (KLF15) is an important negative regulator of cardiac hypertrophy in both experimental models and in man...
April 27, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29672161/tissue-expression-analysis-and-characterization-of-smad3-promoter-in-bovine-myoblasts-and-preadipocytes
#5
Le Zhang, Yue Ning, Peiwei Li, Hongfang Guo, Linsen Zan
The transforming growth factor-β (TGFβ) pathway plays many key roles in regulating numerous biological processes. In addition, the effects of TGFβ are mediated by the transcription factor Smad3. However, the regulation of Smad3 activity is not well understood. In the present study, quantitative real-time PCR revealed that the Smad3 gene was expressed ubiquitously in 11 bovine tissues and displayed different expression patterns between muscle and adipose tissue. We further explored the expression and regulation of Smad3 gene by cloning the bovine Smad3 gene promoter; a dual-luciferase reporter assay identified that the core promoter region -337 to -41 bp was located in a CpG island...
June 2018: DNA and Cell Biology
https://www.readbyqxmd.com/read/29551501/klf15-promotes-transcription-of-klf3-gene-in-bovine-adipocytes
#6
Hongfang Guo, Rajwali Khan, Sayed Haidar Abbas Raza, Yue Ning, Dawei Wei, Sen Wu, Seyed Mahdi Hosseini, Irfan Ullah, Matthew D Garcia, Linsen Zan
The Krüppel-like factors (KLF) family plays an important role in adipogenesis, which is subject to internal hierarchical regulation. KLF3 is a member of KLF family, mainly responsible for adipocyte differentiation and fat deposition. However, the transcriptional regulation of bovine KLF3 gene and its relationship with KLF15 gene remains unclear during bovine adipogenesis. Here, we report that the expression pattern of KLF3 and KLF15 genes during bovine adipogenesis, when KLF15 gene was overexpressed through adenoviral vector (Ad-KLF15) in bovine adipocytes the expression level of KLF3 gene was increased, similarly when KLF15 was down regulated through siRNA the expression level of KLF3 was also reduced...
June 15, 2018: Gene
https://www.readbyqxmd.com/read/29472234/hypoxia-triggers-senp1-sentrin-specific-protease-1-modulation-of-klf15-kruppel-like-factor-15-and-transcriptional-regulation-of-arg2-arginase-2-in-pulmonary-endothelium
#7
Deepesh Pandey, Yohei Nomura, Max C Rossberg, Daijiro Hori, Anil Bhatta, Gizem Keceli, Thorsten Leucker, Lakshmi Santhanam, Larissa A Shimoda, Dan Berkowitz, Lewis Romer
OBJECTIVE: KLF15 (Kruppel-like factor 15) has recently been shown to suppress activation of proinflammatory processes that contribute to atherogenesis in vascular smooth muscle, however, the role of KLF15 in vascular endothelial function is unknown. Arginase mediates inflammatory vasculopathy and vascular injury in pulmonary hypertension. Here, we tested the hypothesis that KLF15 is a critical regulator of hypoxia-induced Arg2 (arginase 2) transcription in human pulmonary microvascular endothelial cells (HPMEC)...
April 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/29456648/immunosuppressive-effects-of-hydroxychloroquine-and-artemisinin-combination-therapy-via-the-nuclear-factor-%C3%AE%C2%BAb-signaling-pathway-in-lupus-nephritis-mice
#8
Ning Liang, Yanchun Zhong, Jie Zhou, Bihao Liu, Ruirui Lu, Yezhi Guan, Qi Wang, Chunlin Liang, Yu He, Yuan Zhou, Jianping Song, Jiuyao Zhou
Lupus nephritis (LN) is one of the most common and severe manifestations of systemic lupus erythematosus, leading to permanent renal damage and chronic kidney disease. Hydroxychloroquine (HCQ) serves a protective role against lupus-associated clinical manifestations and medical complications; however, it results in numerous adverse reactions, limiting its long-term use. The aim of the present study was to investigate the combined effect of HCQ and artemisinin (ART) on LN, and to elucidate the underlying mechanisms...
March 2018: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29408889/kruppel-like-factor-15-is-required-for-the-cardiac-adaptive-response-to-fasting
#9
Keiki Sugi, Paishiun N Hsieh, Olga Ilkayeva, Shamanthika Shelkay, Bridget Moroney, Palvir Baadh, Browning Haynes, Megan Pophal, Liyan Fan, Christopher B Newgard, Domenick A Prosdocimo, Mukesh K Jain
Cardiac metabolism is highly adaptive in response to changes in substrate availability, as occur during fasting. This metabolic flexibility is essential to the maintenance of contractile function and is under the control of a group of select transcriptional regulators, notably the nuclear receptor family of factors member PPARα. However, the diversity of physiologic and pathologic states through which the heart must sustain function suggests the possible existence of additional transcriptional regulators that play a role in matching cardiac metabolism to energetic demand...
2018: PloS One
https://www.readbyqxmd.com/read/29408733/bioinformatics-analysis-of-non-synonymous-variants-in-the-klf-genes-related-to-cardiac-diseases
#10
Katyana Kaline Silva Ferreira, Enéas Ricardo de Morais Gomes, José Luiz de Lima Filho, Carlos Henrique Madeiros Castelletti, Danyelly Bruneska Gondim Martins
Kruppel-like Factors (KLF) are responsible for regulating many genes involved in physiological and pathological processes. They are characterized by three conserved zinc-fingers in the DNA-binding domain, wherein mutations could affect the binding efficiency and transcription regulation. This study aimed to perform bioinformatics analysis to determine the most deleterious non-synonymous variants in KLFs involved in cardiac development and diseases, and their effects over the protein structure and stability...
April 15, 2018: Gene
https://www.readbyqxmd.com/read/29390927/malignant-ewing-like-neoplasm-with-an-ewsr1-klf15-fusion-at-the-crossroads-of-a-myoepithelial-carcinoma-and-a-ewing-like-sarcoma-a-case-report-with-treatment-options
#11
Todd M Stevens, Morad Qarmali, Diana Morlote, Fady M Mikhail, Jeffrey Swensen, Zoran Gatalica, Gene P Siegal, Robert M Conry
We present a case of a malignant Ewing-like neoplasm of the parotid gland in a 20-year-old woman with an EWSR1-KLF15 gene fusion that presented with pulmonary metastasis. Despite the fact that the tumor was essentially immunohistochemically negative for keratins, p63, and p40, we interpret this neoplasm as an unusual form of a high-grade myoepithelial carcinoma based on its focal plasmacytoid cytology, chondromyxoid matrix, SOX10, S100 protein, and calponin expression, and the knowledge that the EWSR1-KLF15 gene fusion has, to date, only been identified in 2 tumors, both myoepithelial carcinomas of the kidney...
January 1, 2018: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29323335/tanshinol-alleviates-impaired-bone-formation-by-inhibiting-adipogenesis-via-klf15-ppar%C3%AE-2-signaling-in-gio-rats
#12
Ya-Jun Yang, Zhu Zhu, Dong-Tao Wang, Xin-le Zhang, Yu-Yu Liu, Wen-Xiu Lai, Yu-Lin Mo, Jin Li, Yan-Long Liang, Zhuo-Qing Hu, Yong-Jie Yu, Liao Cui
Glucocorticoid (GC)-induced osteoporosis (GIO) is characterized by impaired bone formation, which can be alleviated by tanshinol, an aqueous polyphenol isolated from Salvia miltiorrhiza Bunge. In this study we investigated the molecular mechanisms underlying GC-induced modulation of osteogenesis as well as the possibility of using tanshinol to interfere with GIO. Female SD rats aged 4 months were orally administered distilled water (Con), prednisone (GC, 5 mg·kg-1 ·d-1 ), GC plus tanshinol (Tan, 16 mg·kg-1 ·d-1 ) or GC plus resveratrol (Res, 5 mg·kg-1 ·d-1 ) for 14 weeks...
April 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29299121/klf15-promotes-the-proliferation-and-metastasis-of-lung-adenocarcinoma-cells-and-has-potential-as-a-cancer-prognostic-marker
#13
Lihua Gao, Hongmei Qiu, Jian Liu, Yuzhen Ma, Jia Feng, Li Qian, Jianguo Zhang, Yifei Liu, Tingting Bian
Lung adenocarcinoma (LADC)is a general form of non-small cell lung cancer that represents a significant threat to public health worldwide. The 5-year-survival rate for LADC is currently below 15%. The transcription factor KLF15, also called kidney-enriched KLF (KKLF), has been proven to play a role in inhibiting proliferation and diversification of carcinoma cells, including those of the endometrium, pancreas and breast, but the involvement of KLF15 in LADC has not previously been studied. In this study, we compared the in vitro expression of KLF15 in human LADC tissues and adjacent normal lung tissues...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29288718/kr%C3%A3-ppel-like-factor-15-regulator-of-bcaa-metabolism-and-circadian-protein-rhythmicity
#14
REVIEW
Liyan Fan, Paishiun N Hsieh, David R Sweet, Mukesh K Jain
Regulation of nutrient intake, utilization, and storage exhibits a circadian rhythmicity that allows organisms to anticipate and adequately respond to changes in the environment across day/night cycles. The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are important modulators of metabolism and metabolic health - for example, their catabolism yields carbon substrates for gluconeogenesis during periods of fasting. Krüppel-like factor 15 (KLF15) has recently emerged as a critical transcriptional regulator of BCAA metabolism, and the absence of this transcription factor contributes to severe pathologies such as Duchenne muscular dystrophy and heart failure...
April 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29241541/adipose-klf15-controls-lipid-handling-to-adapt-to-nutrient-availability
#15
Keiichiro Matoba, Yuan Lu, Rongli Zhang, Eric R Chen, Panjamaporn Sangwung, Benlian Wang, Domenick A Prosdocimo, Mukesh K Jain
Adipose tissue stores energy in the form of triglycerides. The ability to regulate triglyceride synthesis and breakdown based on nutrient status (e.g., fed versus fasted) is critical for physiological homeostasis and dysregulation of this process can contribute to metabolic disease. Whereas much is known about hormonal control of this cycle, transcriptional regulation is not well understood. Here, we show that the transcription factor Kruppel-like factor 15 (KLF15) is critical for the control of adipocyte lipid turnover...
December 12, 2017: Cell Reports
https://www.readbyqxmd.com/read/29186676/the-circadian-clock-regulates-adipogenesis-by-a-per3-crosstalk-pathway-to-klf15
#16
Abhishek Aggarwal, Maria José Costa, Belén Rivero-Gutiérrez, Lijuan Ji, Stefanie L Morgan, Brian J Feldman
The generation of new adipocytes from precursor cells (adipogenesis) has implications for systemic metabolism and is a commonly used model for studying the process of cell differentiation in vitro. Previous studies from us and others suggested that the peripheral circadian clock can influence adipogenesis in vitro, but the mechanisms driving this activity and the relevance for adipogenesis in vivo are unknown. Here we reveal that mouse adipocyte precursor cells (APCs) contain a circadian clock that oscillates in vivo...
November 28, 2017: Cell Reports
https://www.readbyqxmd.com/read/29180230/glucocorticoids-genes-and-brain-function
#17
REVIEW
Grzegorz R Juszczak, Adrian M Stankiewicz
The identification of key genes in transcriptomic data constitutes a huge challenge. Our review of microarray reports revealed 88 genes whose transcription is consistently regulated by glucocorticoids (GCs), such as cortisol, corticosterone and dexamethasone, in the brain. Replicable transcriptomic data were combined with biochemical and physiological data to create an integrated view of the effects induced by GCs. The most frequently reported genes were Errfi1 and Ddit4. Their up-regulation was associated with the altered transcription of genes regulating growth factor and mTORC1 signaling (Gab1, Tsc22d3, Dusp1, Ndrg2, Ppp5c and Sesn1) and progression of the cell cycle (Ccnd1, Cdkn1a and Cables1)...
March 2, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29179208/klf-15-works-as-an-early-anti-fibrotic-transcriptional-regulator-in-ang-ii-induced-renal-fibrosis-via-down-regulation-of-ctgf-expression
#18
Xiangchen Gu, Dechao Xu, Lili Fu, Yi Wang, Changlin Mei, Xiang Gao
BACKGROUND/AIMS: Angiotensin II (Ang II) has been regarded as an important profibrogenic cytokine in renal fibrosis. Krüppel-like factor 15 (KLF15) has been identified as an important negative transcription factor in renal fibrosis. However, little is known about the role of KLF15 in Ang II-induced renal fibrosis. METHODS: In this study, we randomized mice into a control group, Ang II group or Ang II plus losartan group. KLF15 expression was examined with real-time PCR and immunofluorescence in these groups...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29127073/estrogen-receptor-beta-maintains-expression-of-klf15-to-prevent-cardiac-myocyte-hypertrophy-in-female-rodents
#19
Neil Hoa, Lisheng Ge, Kenneth S Korach, Ellis R Levin
Maintaining a healthy, anti-hypertrophic state in the heart prevents progression to cardiac failure. In humans, angiotensin II (AngII) indirectly and directly stimulates hypertrophy and progression, while estrogens acting through estrogen receptor beta (ERβ) inhibit these AngII actions. The KLF15 transcription factor has been purported to provide anti-hypertrophic action. In cultured neonatal rat cardiomyocytes, we found AngII inhibited KLF1 expression and nuclear localization, substantially prevented by estradiol (E2) or β-LGND2 (β-LGND2), an ERβ agonist...
November 7, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29118722/branched-chain-amino-acid-negatively-regulates-klf15-expression-via-pi3k-akt-pathway
#20
Yunxia Liu, Weibing Dong, Jing Shao, Yibin Wang, Meiyi Zhou, Haipeng Sun
Recent studies have linked branched-chain amino acid (BCAA) with numerous metabolic diseases. However, the molecular basis of BCAA's roles in metabolic regulation remains to be established. KLF15 (Krüppel-like factor 15) is a transcription factor and master regulator of glycemic, lipid, and amino acids metabolism. In the present study, we found high concentrations of BCAA suppressed KLF15 expression while BCAA starvation induced KLF15 expression, suggesting KLF15 expression is negatively controlled by BCAA...
2017: Frontiers in Physiology
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