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https://www.readbyqxmd.com/read/28231341/identification-of-the-er-resident-e3-ubiquitin-ligase-rnf145-as-a-novel-lxr-regulated-gene
#1
Emma C L Cook, Jessica K Nelson, Vincenzo Sorrentino, Duco Koenis, Martina Moeton, Saskia Scheij, Roelof Ottenhoff, Boris Bleijlevens, Anke Loregger, Noam Zelcer
Cellular cholesterol metabolism is subject to tight regulation to maintain adequate levels of this central lipid molecule. Herein, the sterol-responsive Liver X Receptors (LXRs) play an important role owing to their ability to reduce cellular cholesterol load. In this context, identifying the full set of LXR-regulated genes will contribute to our understanding of their role in cholesterol metabolism. Using global transcriptional analysis we report here the identification of RNF145 as an LXR-regulated target gene...
2017: PloS One
https://www.readbyqxmd.com/read/28231275/suppression-of-tgf-%C3%AE-pathway-by-pirfenidone-decreases-extracellular-matrix-deposition-in-ocular-fibroblasts-in-vitro
#2
Thomas Stahnke, Bhavani S Kowtharapu, Oliver Stachs, Klaus-Peter Schmitz, Johannes Wurm, Andreas Wree, Rudolf Friedrich Guthoff, Marina Hovakimyan
In glaucoma surgery, fibrotic processes occur, leading to impairment of liquid outflow. Activated fibroblasts are responsible for postoperative scarring. The transforming growth factor-β (TGF-β) pathway plays a key role in fibroblast function, differentiation and proliferation. The aim of this study was the characterization of the fibrotic potential of two subtypes of primary human ocular fibroblasts and the attempt to inhibit fibrotic processes specifically, without impairing cell viability. For fibrosis inhibition we focused on the small molecule pirfenidone, which has been shown to prevent pulmonary fibrosis by the decrease of the expression of TGF-β1, TGF-β2 and TGF-β3 cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28229933/nuclear-lamins-and-progerin-are-dispensable-for-antioxidant-nrf2-response-to-arsenic-and-cadmium
#3
Kazunori Hashimoto, Rima Majumdar, Yoshiaki Tsuji
Lamins are important constituents of the nuclear inner membrane and provide a platform for transcription factors and chromatin. Progerin, a C-terminal truncated lamin A mutant, causes premature aging termed Hutchinson-Gilford Progeria Syndrome (HGPS). Oxidative stress appears to be involved in the pathogenesis of HGPS, although the mechanistic role of progerin remains elusive. Here we examined whether nuclear lamins are important for a cellular antioxidant mechanism, and whether progerin compromises it. We investigated the activation of nuclear factor-E2-related factor 2 (Nrf2) which regulates various antioxidant genes including heme oxygenase-1 (HMOX1), following exposure to sodium arsenite or cadmium chloride in lamin knockdown human cell lines and primary HGPS human fibroblasts...
February 14, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28229451/honokiol-protects-skin-cells-against-inflammation-collagenolysis-apoptosis-and-senescence-caused-by-cigarette-smoke-damage
#4
Adilson Costa, Gustavo Facchini, Ana Lúcia T A Pinheiro, Michelle S da Silva, Michael Y Bonner, Jack Arbiser, Samara Eberlin
BACKGROUND: Pollution, especially cigarette smoke, is a major cause of skin damage. OBJECTIVES: To assess the effects of the small molecule polyphenol, honokiol, on reversing cigarette smoke-induced damage in vitro to relevant skin cells. METHODS: Keratinocytes (HaCat) cultures were exposed to cigarette smoke and, after 48 hours, IL-1α and IL-8 were measured in cell supernatants. Moreover, TIMP-2 production, apoptosis rate, and senescence β-galactosidase expression were evaluated in primary human foreskin fibroblasts (HFF-1) cultures...
February 22, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28228400/inhibiting-aerobic-glycolysis-suppresses-renal-interstitial-fibroblasts-activation-and-renal-fibrosis
#5
Hao Ding, Lei Jiang, Jing Xu, Feng Bai, Yang Zhou, Qi Yuan, Jing Luo, Ke Zen, Junwei Yang
Chronic kidney diseases (CKD) generally lead to renal fibrosis. Despite great progresses have been made in identifying molecular mediators of fibrosis, the mechanism that governs renal fibrosis remains unclear and so far no effective therapeutic anti-fibrosis strategy is available. Here we demonstrated that a switch of metabolism from oxidative phosphorylation to aerobic glycolysis (Warburg effect) in renal fibroblasts was the primary feature of fibroblast activation during renal fibrosis, and that suppressing renal fibroblast aerobic glycolysis could significantly reduce renal fibrosis...
February 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28225655/mnte-2-pyp-treatment-or-nox4-inhibition-protects-against-radiation-induced-damage-in-mouse-primary-prostate-fibroblasts-by-inhibiting-the-tgf-beta-1-signaling-pathway
#6
Arpita Chatterjee, Elizabeth A Kosmacek, Rebecca E Oberley-Deegan
Prostate cancer patients who undergo radiotherapy frequently suffer from side effects caused by radiation-induced damage to normal tissues adjacent to the tumor. Exposure of these normal cells during radiation treatment can result in tissue fibrosis and cellular senescence, which ultimately leads to postirradiation-related chronic complications including urinary urgency and frequency, erectile dysfunction, urethral stricture and incontinence. Radiation-induced reactive oxygen species (ROS) have been reported as the most potent causative factor for radiation damage to normal tissue...
February 22, 2017: Radiation Research
https://www.readbyqxmd.com/read/28225071/resolution-of-tlr2-induced-inflammation-through-manipulation-of-metabolic-pathways-in-rheumatoid-arthritis
#7
Trudy McGarry, Monika Biniecka, Wei Gao, Deborah Cluxton, Mary Canavan, Siobhan Wade, Sarah Wade, Lorna Gallagher, Carl Orr, Douglas J Veale, Ursula Fearon
During inflammation, immune cells activated by toll-like receptors (TLRs) have the ability to undergo a bioenergetic switch towards glycolysis in a manner similar to that observed in tumour cells. While TLRs have been implicated in the pathogenesis of rheumatoid arthritis (RA), their role in regulating cellular metabolism in synovial cells, however, is still unknown. In this study, we investigated the effect of TLR2-activation on mitochondrial function and bioenergetics in primary RA-synovial fibroblast cells (RASFC), and further determined the role of glycolytic blockade on TLR2-induced inflammation in RASFC using glycolytic inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO)...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28223126/targeted-inhibition-of-hdac8-increases-the-doxorubicin-sensitivity-of-neuroblastoma-cells-via-up-regulation-of-mir-137
#8
Gang Zhao, Guoliang Wang, Hongmin Bai, Tiandong Li, Fanghe Gong, Huan Yang, Jinchong Wen, Weimin Wang
Histone deacetylases (HDACs) have been suggested to be potential therapeutic targets for cancer treatment. Recent studies revealed that HDAC8 expression was associated with poor prognostic markers and poor overall survival rate of neuroblastoma (NB). Our present study revealed that among the four members of class I HDACs, HDAC8 is significantly over expressed in NB cells as compared with the normal fibroblast 3T3 cells or primary normal human astrocytes (NHA) cells. Targeted inhibition of HDAC8 by its specific siRNA (si-HDAC8) can inhibit the in vitro growth of NB cells...
February 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28222755/wd-repeat-protein-wdr13-is-a-novel-transcriptional-regulator-of-c-jun-and-modulates-intestinal-homeostasis-in-mice
#9
Vijay Pratap Singh, Saritha Katta, Satish Kumar
BACKGROUND: WDR13 is a member of the WD repeat protein family and is expressed in several tissues of human and mice. Previous studies in our laboratory showed that the lack of this gene in mice resulted in mild obesity, hyperinsulinemia, enhanced beta cell proliferation and protection from inflammation. However, the molecular mechanism of WDR13 action is not well understood. METHODS: In the present study, we used AOM/DSS to induce colitis-mediated colorectal tumor after establishing expression of Wdr13 gene in colon...
February 21, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28222255/stemness-signature-of-equine-marrow-derived-mesenchymal-stem-cells
#10
Morteza Zahedi, Abbas Parham, Hesam Dehghani, Hossein Kazemi Mehrjerdi
Background: Application of competent cells such as mesenchymal stem cells (MSCs) for treatment of musculoskeletal disorders in equine athletes is increasingly needed. Moreover, similarities of horse and human in size, load and types of joint injuries, make horse as a good model for MSCs therapy studies. This study was designed to isolate and characterize stemness signature of equine bone marrow-derived mesenchymal stem cells (BM-MSCs). Methods: BM of three mares was aspirated and the mononuclear cells (MNCs) were isolated using density gradient...
February 28, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/28218424/p16-ink4a-enhances-the-transcriptional-and-the-apoptotic-functions-of-p53-through-dna-dependent-interaction
#11
Huda H Al-Khalaf, Shreeram C Nallar, Dhananjaya V Kalvakolanu, Abdelilah Aboussekhra
p16(INK4A) and p53 are two important tumor suppressor proteins that play essential roles during cell proliferation and aging through regulating the expression of several genes. Here, we report that p16(INK4A) and p53 co-regulate a plethora of transcripts. Furthermore, both proteins colocalize in the nucleus of human primary skin fibroblasts and breast luminal cells, and form a heteromer whose level increases in response to genotoxic stress as well as aging of human fibroblasts and various mouse organs. CDK4 is also present in this heteromeric complex, which is formed only in the presence of DNA both in vitro using pure recombinant proteins and in vivo...
February 20, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28214209/expression-and-promoter-dna-methylation-of-mlh1-in-colorectal-cancer-and-lung-cancer
#12
Yunxia Ma, Yuan Chen, Iver Petersen
AIMS: Aberrant DNA methylation is a common molecular feature in human cancer. The aims of this study were to analyze the methylation status of MLH1, one of the DNA mismatch repair (MMR) genes, in human colorectal and lung cancer and to evaluate its clinical relevance. METHODS: The expression of MLH1 was analyzed in 8 colorectal cancer (CRC) and 8 lung cancer cell lines by real-time RT-PCR and western blotting. The MLH1 protein expression was evaluated by immunohistochemistry on tissue microarrays including 121 primary CRC and 90 lung cancer patient samples...
January 22, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213002/a-phase-ii-trial-of-dovitinib-in-previously-treated-advanced-pleural-mesothelioma-the-ontario-clinical-oncology-group
#13
Scott A Laurie, Desiree Hao, Natasha B Leighl, John Goffin, Abderrahim Khomani, Ashish Gupta, Christina L Addison, Anita Bane, Jean Seely, Marc L Filion, Gregory R Pond, Mark N Levine
OBJECTIVES: Following failure of a platinum-antifolate combination regimen, there is no standard therapy for advanced malignant pleural mesothelioma (MPM). The fibroblast growth factor receptor (FGFR) signaling pathways may be a relevant target in MPM. Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFRs, and could be active in MPM. METHODS: This open-label multicentre phase II trial [NCT01769547] enrolled fit, consenting adult patients with advanced MPM who had previously received platinum-antifolate combination chemotherapy and up to one additional line of systemic therapy...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28211632/amp-activated-protein-kinase-activator-a-769662-increases-intracellular-calcium-and-atp-release-from-astrocytes-in-an-ampk-independent-manner
#14
Julia M Vlachaki Walker, Josephine L Robb, Ana M Cruz, Amrinder Malhi, Paul G Weightman Potter, Michael L J Ashford, Rory J McCrimmon, Kate L J Ellacott, Craig Beall
AIM: Astrocytes are the main sources of extracellular ATP (eATP) within the brain, which functions as a gliotransmitter, capable of modulating neuronal and astrocytic activity. These cells play an important role in regulating energy homeostasis partly via astrocyte-derived ATP. Given the role of AMPK in regulating intracellular ATP levels, we hypothesised that AMPK may alter ATP release from astrocytes. METHODS: Measurements of ATP release were made from human U373 astrocytoma cells, primary mouse hypothalamic (HTAS) and cortical astrocytes (CRTAS) and wild type and AMPK α1/α2 null mouse embryonic fibroblasts (MEFs)...
February 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28211546/differential-effects-of-hormones-on-cellular-metabolism-in-keratoconus-in-vitro
#15
Tina B McKay, Jesper Hjortdal, Henrik Sejersen, Dimitrios Karamichos
Keratoconus (KC) is a corneal thinning disease with an onset commonly immediately post-puberty and stabilization by 40 to 50 years of age. The role of hormones in regulating corneal tissue structure in homeostatic and pathological conditions is unknown. Our group recently linked altered hormone levels to KC. Our current study sought to investigate and delineate the effects of exogenous hormones, such as androgen, luteotropin, and estrogen, on corneal stroma bioenergetics. We utilized our established 3D in vitro model to characterize the effects of DHEA, prolactin, 17β-estradiol on insulin-growth factor-1 and -2 (IGF-1, -2) signaling and metabolic function in primary corneal fibroblasts from healthy controls (HCFs) and KC patients (HKCs)...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28211118/transcriptional-and-cell-cycle-alterations-mark-aging-of-primary-human-adipose-derived-stem-cells
#16
Xiaoyin Shan, Cleresa Roberts, Eun Ji Kim, Ariana Brenner, Gregory Grant, Ivona Percec
Adult stem cells play a critical role in the maintenance of tissue homeostasis and prevention of aging. While the regenerative potential of stem cells with low cellular turnover, such as adipose-derived stem cells (ASC), is increasingly recognized, the study of chronological aging in ASCs is technically difficult, and remains poorly understood. Here, we employ our model of chronological aging in primary human ASCs to examine genome-wide transcriptional networks. We demonstrate first that the transcriptome of aging ASCs is distinctly more stable than that of age-matched fibroblasts, and further, that age-dependent modifications in cell cycle progression and translation initiation specifically characterize aging ASCs in conjunction with increased nascent protein synthesis and a distinctly shortened G1 phase...
February 17, 2017: Stem Cells
https://www.readbyqxmd.com/read/28207890/mucosal-stromal-fibroblasts-markedly-enhance-hiv-infection-of-cd4-t-cells
#17
Jason A Neidleman, Joseph C Chen, Nargis Kohgadai, Janis A Müller, Anders Laustsen, Karthiga Thavachelvam, Karen S Jang, Christina M Stürzel, Jennifer J Jones, Christina Ochsenbauer, Avantika Chitre, Ma Somsouk, Maurice M Garcia, James F Smith, Ruth M Greenblatt, Jan Münch, Martin R Jakobsen, Linda C Giudice, Warner C Greene, Nadia R Roan
Understanding early events of HIV transmission within mucosal tissues is vital for developing effective prevention strategies. Here, we report that primary stromal fibroblasts isolated from endometrium, cervix, foreskin, male urethra, and intestines significantly increase HIV infection of CD4+ T cells-by up to 37-fold for R5-tropic HIV and 100-fold for X4-tropic HIV-without themselves becoming infected. Fibroblasts were more efficient than dendritic cells at trans-infection and mediate this response in the absence of the DC-SIGN and Siglec-1 receptors...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28207886/connective-tissue-growth-factor-is-not-necessary-for-haze-formation-in-excimer-laser-wounded-mouse-corneas
#18
Xiaodi Feng, Liya Pi, Sriniwas Sriram, Gregory S Schultz, Daniel J Gibson
We sought to determine if connective tissue growth factor (CTGF) is necessary for the formation of corneal haze after corneal injury. Mice with post-natal, tamoxifen-induced, knockout of CTGF were subjected to excimer laser phototherapeutic keratectomy (PTK) and the corneas were allowed to heal. The extent of scaring was observed in non-induced mice, heterozygotes, and full homozygous knockout mice and quantified by macrophotography. The eyes from these mice were collected after euthanization for re-genotyping to control for possible Cre-mosaicism...
2017: PloS One
https://www.readbyqxmd.com/read/28206988/inhibition-of-autophagy-blocks-cathepsins-tbid-mitochondrial-apoptotic-signaling-pathway-via-stabilization-of-lysosomal-membrane-in-ischemic-astrocytes
#19
Xian-Yong Zhou, Yu Luo, Yong-Ming Zhu, Zhi-He Liu, Thomas A Kent, Jia-Guo Rong, Wei Li, Shi-Gang Qiao, Min Li, Yong Ni, Kazumi Ishidoh, Hui-Ling Zhang
Our previous study and others have demonstrated that autophagy is activated in ischemic astrocytes and contributes to astrocytic cell death. However, the mechanisms of ischemia-induced autophagy remain largely unknown. In this study, we established a rat's model of permanent middle cerebral artery occlusion (pMCAO) and an in vitro oxygen and glucose deprivation (OGD) model. Autophagy was inhibited by either pharmacological treatment with 3-methyladenine (3-MA) and wortmannin (Wort) or genetic treatment with knockdown of Atg5 in primary cultured astrocytes and knockout of Atg5 in mouse embryonic fibroblast (MEF) cells, respectively...
February 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28202805/chenodeoxycholic-acid-stimulates-glucagon-like-peptide-1-secretion-in-patients-after-roux-en-y-gastric-bypass
#20
Signe Nielsen, Maria S Svane, Rune E Kuhre, Trine R Clausen, Viggo B Kristiansen, Jens F Rehfeld, Jens J Holst, Sten Madsbad, Kirstine N Bojsen-Moller
Postprandial secretion of glucagon-like peptide-1 (GLP-1) is enhanced after Roux-en-Y gastric bypass (RYGB), but the precise molecular mechanisms explaining this remain poorly understood. Plasma concentrations of bile acids (BAs) increase after RYGB, and BAs may act as molecular enhancers of GLP-1 secretion through activation of TGR5-receptors. We aimed to evaluate GLP-1 secretion after oral administration of the primary bile acid chenodeoxycholic acid (CDCA) and the secondary bile acid ursodeoxycholic acid (UDCA) (which are available for oral use) in RYGB-operated participants...
February 2017: Physiological Reports
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