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Fibroblast autophagy

Christian Galasso, Genoveffa Nuzzo, Christophe Brunet, Adrianna Ianora, Angela Sardo, Angelo Fontana, Clementina Sansone
Marine dinoflagellates are a valuable source of bioactive molecules. Many species produce cytotoxic compounds and some of these compounds have also been investigated for their anticancer potential. Here, we report the first investigation of the toxic dinoflagellate Alexandrium minutum as source of water-soluble compounds with antiproliferative activity against human lung cancer cells. A multi-step enrichment of the phenol⁻water extract yielded a bioactive fraction with specific antiproliferative effect (IC50 = 0...
December 12, 2018: Marine Drugs
Biserka Relic, Edith Charlier, Celine Deroyer, Olivier Malaise, Yannick Crine, Sophie Neuville, Philippe Gillet, Dominique de Seny, Michel G Malaise
Phosphorylation of p62/SQSTM1 (p62) on Serine 349 (P-Ser349 p62) as well as proteasome dysfunction have been shown to activate the cell protective Keap1/Nrf2 pathway. We showed previously that BAY 11-7085-induced human synovial fibroblast cell death includes autophagy and p62 downregulation. In this work, we have studied expression of P-Ser349 p62 in human synovial fibroblasts. Results showed that P-Ser349 p62 was not detected in synovial cell extracts unless cells were cultured in the presence of proteasome inhibitor (MG132)...
November 9, 2018: Oncotarget
Xiaohua Tan, Hongmei Zhu, Qianyu Tao, Lisha Guo, Tianfang Jiang, Le Xu, Ruo Yang, Xiayu Wei, Jin Wu, Xiaokun Li, Jin-San Zhang
Ischemia-reperfusion (I/R) is a common cause of acute kidney injury (AKI), which is associated with high mortality and poor outcomes. Autophagy plays important roles in the homeostasis of renal tubular cells (RTCs) and is implicated in the pathogenesis of AKI, although its role in the process is complex and controversial. Fibroblast growth factor 10 (FGF10), a multifunctional FGF family member, was reported to exert protective effect against cerebral ischemia injury and myocardial damage. Whether FGF10 has similar beneficial effect, and if so whether autophagy is associated with the potential protective activity against AKI has not been investigated...
2018: Frontiers in Genetics
Yuhui Wu, Junlin Yao, Jiansheng Xie, Zhen Liu, Yubin Zhou, Hongming Pan, Weidong Han
Autophagy is an evolutionarily conserved catabolic process that eliminates harmful components through lysosomal degradation. In addition to its role in maintaining cellular homeostasis, autophagy is critical to pathological processes, such as inflammation and cancer. Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer that develops from long-standing colitis in inflammatory bowel disease (IBD) patients. Accumulating evidence indicates that autophagy of microenvironmental cells plays different but vital roles during tumorigenesis and CAC development...
2018: Signal Transduction and Targeted Therapy
KaHo Leung, Kasturi Chakraborty, Anand Saminathan, Yamuna Krishnan
Lysosomes are multifunctional, subcellular organelles with roles in plasma membrane repair, autophagy, pathogen degradation and nutrient sensing. Dysfunctional lysosomes underlie Alzheimer's disease, Parkinson's disease and rare lysosomal storage diseases, but their contributions to these pathophysiologies are unclear. Live imaging has revealed lysosome subpopulations with different physical characteristics including dynamics, morphology or cellular localization. Here, we chemically resolve lysosome subpopulations using a DNA-based combination reporter that quantitatively images pH and chloride simultaneously in the same lysosome while retaining single-lysosome information in live cells...
December 3, 2018: Nature Nanotechnology
Fan Wang, Rui Liang, Benjamin Soibam, Jin Yang, Yu Liu
Serum starvation is widely used in cell biology to trigger cell cycle arrest, apoptosis, autophagy, and metabolic adaptations. Serum starvation-related molecular events have been well characterized at protein level but not at transcript level: how long non-coding RNAs contribute to the regulation of protein-coding genes is largely unknown. Here, we captured the lncRNA transcriptome in serum starved mouse embryonic fibroblasts and identified three main modes of action: cis-acting/coregulatory, trans-acting, and "miRNA-carrier"...
November 29, 2018: Biochimica et biophysica acta. Gene regulatory mechanisms
Yujie Dai, Jingjing Ding, Wen Yin, Yuzhu He, Fei Yu, Cong Ye, Shaoxian Hu, Yikai Yu
Tumor Necrosis Factor-alpha (TNF- α ) was reported to increase autophagy in rheumatoid arthritis human fibroblast-like synovial cell (RA-HFLS). We investigated different levels of TNF- α exposed to RA-HFLS by focusing on the relationship of autophagy and apoptosis. RA-HFLS and normal human fibroblast-like synovial cell (HFLS) were stimulated by TNF- α in the presence or the absence of 3-methyladenine (3-MA) or chloroquine (CQ). Cell apoptosis was detected by flow cytometry. Autophagy was determined through the expression levels of LC3, Beclin1, and P62 measured by Western Blot analysis as well as Confocal Laser Scanning Microscopy...
2018: BioMed Research International
Le Chang, Xin Feng, Wei Gao
Fibroblast-like synoviocytes (FLSs), with their tumor-like proliferation, play an important role in rheumatoid arthritis (RA), and interleukin-17 (IL-17) participates in RA pathology by affecting FLSs. The aims of this study were to investigate the effects of IL-17 on the proliferation and autophagy of FLSs and the role of signal transducer and activator of transcription-3 (STAT3) in RA. FLSs were treated with IL-17 at different concentrations (0, 1, 10, and 20 ng/mL); then, autophagy was assayed with western blotting, immunofluorescence and transmission electron microscopy...
November 26, 2018: Connective Tissue Research
Shufen Yang, Rizwanguli Abdulla, Chen Lu, Ling Zhang
BACKGROUND/AIMS: Renal interstitial fibrosis (RIF) is a common feature that facilitates the progression of chronic kidney disease (CKD), and emerging lines of evidence suggest that microRNA-376b (miR-376b) is capable of promoting RIF. In this study, we examined collagen deposition in kidney tissues, the autophagy and mitochondrial reactive oxygen species (ROS) of macrophages, and the apoptosis of kidney fibroblasts (KFBs) after the promotion or suppression of endogenous miR-376b in cultured macrophages and renal fibroblasts obtained from mice with CKD...
November 23, 2018: Kidney & Blood Pressure Research
Ching-Ju Hsiao, Chia-Hsiang Chang, Ridwan Babatunde Ibrahim, I-Hsuan Lin, Chun-Hung Wang, Won-Jing Wang, Jin-Wu Tsai
The primary cilium is a tiny cell protrusion known to transduce key extracellular signals, including the sonic hedgehog pathway, which activates Gli transcription factors for various cellular functions. To understand the significance of Gli2 transcription factor in fibroblasts, we establish a Gli2 knockout NIH3T3 cell line by CRISPR/Cas9 technology. Surprisingly, NIH3T3 fibroblasts lacking Gli2 expression through gene knockout or RNA interference possess longer primary cilia after stimulation of ciliogenesis by serum starvation...
November 21, 2018: Journal of Cell Science
Peng Zhang, Yinglu Guan, Jiajie Chen, Xiang Li, Bradley K McConnell, Wei Zhou, Krishna M Boini, Yang Zhang
Accumulating evidence indicates a critical role of autophagy in regulating vascular smooth muscle cell (SMC) homeostasis in atherogenesis. However, little is known about the modulatory role of autophagy in PDGF-BB-induced SMC transition towards the synthetic phenotype and extracellular matrix remodeling. We recently demonstrated that acid sphingomyelinase (ASM, encoded by Smpd1 gene) controls autophagy maturation in coronary arterial SMCs. Here, we demonstrate that PDGF-BB stimulation causes a myofibroblast-like non-canonical synthetic phenotype transition in Smpd1-/- SMCs...
November 19, 2018: Cell Death & Disease
Yingfeng Lu, Rui Li, Junyi Zhu, Yanqing Wu, Duohui Li, Lupeng Dong, Yiyang Li, Xin Wen, Fangzheng Yu, Hongyu Zhang, Xiao Ni, Shenghu Du, Xiaokun Li, Jian Xiao, Jian Wang
Seeking for effective drugs which are beneficial to facilitating axonal regrowth and elongation after peripheral nerve injury (PNI) has gained extensive attention. Fibroblast growth factor 21 (FGF21) is a metabolic factor that regulates blood glucose and lipid homeostasis. However, there is little concern for the potential protective effect of FGF21 on nerve regeneration after PNI and revealing related molecular mechanisms. Here, we firstly found that exogenous FGF21 administration remarkably promoted functional and morphologic recovery in a rat model of sciatic crush injury, manifesting as persistently improved motor and sensory function, enhanced axonal remyelination and regrowth and accelerated Schwann cells (SCs) proliferation...
November 18, 2018: Journal of Cellular and Molecular Medicine
Azam Hosseinzadeh, Seyed Ali Javad-Moosavi, Russel J Reiter, Rasoul Yarahmadi, Habib Ghaznavi, Saeed Mehrzadi
Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease associated with disruption of alveolar epithelial cell layer and expansion of fibroblasts/myofibroblasts. Excessive levels of oxidative/nitrosative stress, induction of apoptosis, and insufficient autophagy may be involved in IPF pathogenesis; hence, the targeting of these pathways may ameliorate IPF. Areas covered: We describe the ameliorative effect of melatonin on IPF. We summarize the research on IPF pathogenesis with a focus on oxidative/nitrosative stress, autophagy and apoptosis pathways and discuss the potential effects of melatonin on these pathways...
December 2018: Expert Opinion on Therapeutic Targets
Mojgan Karimabad Noroozi, Mehdi Mahmoodi, Abdolah Jafarzadeh, Ali Darekordi, Mohamad Reza Hajizadeh, Gholamhossein Hassanshahi
The indole-3-carbinol (I3C) displays anti-proliferative and anti-cancer activities against human cancer cells. Cellular proliferation is an important event associated with cancer development and continued progression. This manifest is described by altered expression and/or functions of cell cycle related proteins. The constitutive activation of many signal transduction pathways also stimulates cell growth. The immediate stages in tumor development are accompanied by a fibrogenic response and the progression of a hypoxic environment, is in favor of the survival and proliferatory functions of cancer stem cells...
November 16, 2018: Mini Reviews in Medicinal Chemistry
Insung Kang, Byung-Chul Lee, Jin Young Lee, Jae-Jun Kim, Eun-Ah Sung, Seung Eun Lee, Nari Shin, Soon Won Choi, Yoojin Seo, Hyung-Sik Kim, Kyung-Sun Kang
We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite...
November 14, 2018: Experimental & Molecular Medicine
Bela Ozsvari, John R Nuttall, Federica Sotgia, Michael P Lisanti
Here, we employed a "senolytic" assay system as a screening tool, with the goal of identifying and repurposing FDA-approved antibiotics, for the targeting of the senescent cell population. Briefly, we used two established human fibroblast cell lines (MRC-5 and/or BJ) as model systems to induce senescence, via chronic treatment with a DNA-damaging agent, namely BrdU (at a concentration of 100 μM for 8 days). Cell viability was then monitored by using the SRB assay, to measure protein content. As a consequence of this streamlined screening strategy, we identified Azithromycin and Roxithromycin as two novel clinically-approved senolytic drugs...
November 14, 2018: Aging
Asmaa A Alsousi, Orisa J Igwe
Reactive oxygen species (ROS) are implicated to play a role in initiating rheumatoid arthritis (RA) pathogenesis. We have investigated the mechanism(s) by which essential redox-active trace metals (RATM) may induce cell proliferation and cell death in rabbit synovial fibroblasts. These fibroblast-like synovial (FLS) cells, which express Toll-like receptor 4 (TLR4), were used as a model system that plays a role in potentially initiating RA through oxidative stress. Potassium peroxychromate (PPC, [Cr5+ ]), ferrous chloride (FeCl2 , [Fe2+ ]), and cuprous chloride (CuCl, [Cu+ ]) in the indicated valency states were used as exogenous pro-oxidants that can induce oxidative stress through TLR4 coupled activation that also causes HMGB1 release...
November 6, 2018: Experimental Cell Research
Enxiang Zhang, Xiaotong Lu, Shutao Yin, Mingzhu Yan, Shangyun Lu, Lihong Fan, Hongbo Hu
Induction of programmed cell death, mainly apoptosis (lipoapoptosis) is a major cellular consequence of the lipotoxicity, a harmful effect resulting from the overload of lipids. Both Endoplasmic reticulum (ER) stress and autophagy have been suggested to play important role in the regulation of lipoapoptosis. However, the exact mechanisms underlying lipoapoptosis remain unclear. In the present study, we aimed to investigate the functional role of Bax/Bak in lipoapoptosis using mouse embryonic fibroblasts (MEFs) cell culture model...
November 5, 2018: Food and Chemical Toxicology
Shashank Rai, Maryam Arasteh, Matthew Jefferson, Timothy Pearson, Yingxue Wang, Weijiao Zhang, Bertalan Bicsak, Devina Divekar, Penny P Powell, Ronald Nauman, Naiara Beraza, Simon R Carding, Oliver Florey, Ulrike Mayer, Thomas Wileman
Macroautophagy/autophagy delivers damaged proteins and organelles to lysosomes for degradation, and plays important roles in maintaining tissue homeostasis by reducing tissue damage. The translocation of LC3 to the limiting membrane of the phagophore, the precursor to the autophagosome, during autophagy provides a binding site for autophagy cargoes, and facilitates fusion with lysosomes. An autophagy-related pathway called LC3-associated phagocytosis (LAP) targets LC3 to phagosome and endosome membranes during uptake of bacterial and fungal pathogens, and targets LC3 to swollen endosomes containing particulate material or apoptotic cells...
November 7, 2018: Autophagy
Ruhui Yang, Zhaoxia Song, Songquan Wu, Zhe Wei, Yini Xu, Xiangchun Shen
BACKGROUND AND AIMS: Cardiac fibrosis after myocardial infarction (MI) is involved in fibroblast transforming and differentiating into myofibroblast phenoconversion, however, the underlying mechanisms are poorly understood. Toll-like receptor 4 (TLR4)-mediated pathogen-associated molecular patterns are key factors that deteriorate cardiac remodelling after MI. Moreover, autophagy has dual roles in cell survival in myocardial tissues after MI. We evaluated the relationship between TLR4 signalling and cardiac myofibroblast transformation-differentiation after MI in vivo and in vitro and analysed the role of autophagy...
October 19, 2018: Atherosclerosis
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