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Fibroblast autophagy

Jingting Zhang, Tao Ruan, Tianyu Sheng, Jiongjiong Wang, Jing Sun, Jin Wang, Richard A Prinz, Daxin Peng, Xiufan Liu, Xiulong Xu
The non-structural protein 1 (NS1) of different influenza A virus (IAV) strains can differentially regulate the activity of c-Jun terminal kinase (JNK) and PI-3 kinase (PI3K). Whether varying JNK and PI3K activation impacts autophagy and IAV replication differently remains uncertain. Here we report that H5N1 (A/mallard/Huadong/S/2005) influenza A virus induced functional autophagy, as evidenced by increased LC3 lipidation and decreased p62 levels, and the presence of autolysosomes in chicken fibroblast cells...
October 10, 2018: Virology
Hendrik Folkerts, Susan Hilgendorf, Edo Vellenga, Edwin Bremer, Valerie R Wiersma
Autophagy is a crucial recycling process that is increasingly being recognized as an important factor in cancer initiation, cancer (stem) cell maintenance as well as the development of resistance to cancer therapy in both solid and hematological malignancies. Furthermore, it is being recognized that autophagy also plays a crucial and sometimes opposing role in the complex cancer microenvironment. For instance, autophagy in stromal cells such as fibroblasts contributes to tumorigenesis by generating and supplying nutrients to cancerous cells...
October 9, 2018: Medicinal Research Reviews
Kyle A Metz, Xinchen Teng, Isabelle Coppens, Heather M Lamb, Bart E Wagner, Jill A Rosenfeld, Xianghui Chen, Yu Zhang, Hee Jong Kim, Michael E Meadow, Tim Sen Wang, Edda D Haberlandt, Glenn W Anderson, Esther Leshinsky-Silver, Weimin Bi, Thomas C Markello, Marsha Pratt, Nawal Makhseed, Adolfo Garnica, Noelle R Danylchuk, Thomas A Burrow, Parul Jayakar, Dianalee McKnight, Satish Agadi, Hatha Gbedawo, Christine Stanley, Michael Alber, Isabelle Prehl, Katrina Peariso, Min Tsui Ong, Santosh R Mordekar, Michael J Parker, Daniel Crooks, Pankaj B Agrawal, Gerard T Berry, Tobias Loddenkemper, Yaping Yang, Gustavo H B Maegawa, Abdel Aouacheria, Janet G Markle, James A Wohlschlegel, Adam L Hartman, J Marie Hardwick
OBJECTIVE: Several small case series identified KCTD7 mutations in patients with a rare autosomal recessive disorder designated progressive myoclonic epilepsy (EPM3) and neuronal ceroid lipofuscinosis (CLN14). Despite the name KCTD (potassium channel tetramerization domain), KCTD protein family members lack predicted channel domains. We sought to translate insight gained from yeast studies to uncover disease mechanisms associated with deficiencies in KCTD7 of unknown function. METHODS: Novel KCTD7 variants in new and published patients were assessed for disease causality using genetic analyses, cell-based functional assays of patient fibroblasts and knockout yeast, and electron microscopy of patient samples...
October 8, 2018: Annals of Neurology
Jinfang Bao, Yingfeng Shi, Min Tao, Na Liu, Shougang Zhuang, Weijie Yuan
Autophagy has been identified as a cellular process of bulk degradation of cytoplasmic components and its persistent activation is critically involved in the renal damage induced by ureteral obstruction. However, the role and underlying mechanisms of autophagy in hyperuricemic nephropathy (HN) remains unknown. In this study, we observed that inhibition of autophagy by 3-methyladenine (3-MA) abolished uric acid-induced differentiation of renal fibroblasts to myofibroblasts and activation of transforming growth factor-β1 (TGF-β1), epidermal growth factor receptor (EGFR), and Wnt signaling pathways in cultured renal interstitial fibroblasts...
October 7, 2018: Clinical Science (1979-)
Juan M Suárez-Rivero, Mario de la Mata, Ana Delgado Pavón, Marina Villanueva-Paz, Suleva Povea-Cabello, David Cotán, Mónica Álvarez-Córdoba, Irene Villalón-García, Patricia Ybot-González, Joaquín J Salas, Ovidio Muñiz, Mario D Cordero, José A Sánchez-Alcázar
Familial Hypercholesterolemia (FH) is an autosomal co-dominant genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol levels and increased risk for premature cardiovascular disease. Here, we examined FH pathophysiology in skin fibroblasts derived from FH patients harboring heterozygous mutations in the LDL-receptor. Fibroblasts from FH patients showed a reduced LDL-uptake associated with increased intracellular cholesterol levels and coenzyme Q10 (CoQ10 ) deficiency, suggesting dysregulation of the mevalonate pathway...
October 5, 2018: Biochimica et biophysica acta. Molecular basis of disease
Sensen Shen, Li Yang, Linnan Li, Yu Bai, Huwei Liu
Autophagy is of great significance in maintaining cellular homeostasis. Aberrant autophagy has been reported to contribute to the disease aetiology of metabolic syndrome, especially several key lysosomal storage disorders. However, the molecular mechanisms and the correlation between autophagy and lipid metabolism remains unclear. This study was designed and aimed to reveal the alteration of lipid metabolism in response to the autophagy induced by nutrient stress to give new insights into the molecular mechanisms between autophagy and lipid metabolism...
December 11, 2018: Analytica Chimica Acta
Margherita Leonardi, Eluisa Perna, Serena Tronnolone, David Colecchia, Mario Chiariello
Macroautophagy/autophagy is one of the major responses to stress in eukaryotic cells and is implicated in several pathological conditions such as infections, neurodegenerative diseases and cancer. Interestingly, cancer cells take full advantage of autophagy both to support tumor growth in adverse microenvironments and to oppose damages induced by anti-neoplastic therapies. Importantly, different human oncogenes are able to modulate this survival mechanism to support the transformation process, ultimately leading to 'autophagy addiction'...
October 5, 2018: Autophagy
Alan Diot, Thomas Agnew, Jeremy Sanderson, Chunyan Liao, Janet Carver, Ricardo Pires das Neves, Rajeev Gupta, Yanping Guo, Caroline Waters, Sharon Seto, Matthew J Daniels, Eszter Dombi, Tiffany Lodge, Karl Morten, Suzannah A Williams, Tariq Enver, Francisco J Iborra, Marcela Votruba, Joanna Poulton
Background: Autosomal dominant optic atrophy (ADOA) is usually caused by mutations in the essential gene, OPA1. This encodes a ubiquitous protein involved in mitochondrial dynamics, hence tissue specificity is not understood. Dysregulated mitophagy (mitochondria recycling) is implicated in ADOA, being increased in OPA1 patient fibroblasts. Furthermore, autophagy may be increased in retinal ganglion cells (RGCs) of the OPA1Q285STOP mouse model. Aims: We developed a mouse model for studying mitochondrial dynamics in order to investigate mitophagy in ADOA...
2018: Frontiers in Cell and Developmental Biology
Sensen Shen, Linnan Li, Songyue Li, Yu Bai, Huwei Liu
Autophagy is the lysosomal-dependent degradation process of intracellular substances in adaptation to environmental or developmental changes. It plays an essential role in maintaining cellular homeostasis while its dysfunction is involved in various human diseases. The regulation of autophagy has attracted more and more attention with the promise for improving treatment of diseases as a potential therapeutic target. Metal-organic frameworks (MOFs), as emerging biomaterials, have been investigated in the biological and biomedical fields in recent years...
October 4, 2018: Nanoscale
Yaping Wang, Panpan Chen, Lihan Wang, Jing Zhao, Zhiwei Zhong, Yingchao Wang, Jifeng Xu
BACKGROUND/AIMS: Histone deacetylases (HDACs) play a critical role in the regulation of gene transcription, cardiac development, and diseases. The aim of this study was to investigate whether the inhibition of HDACs improves cardiac remodeling and its underlying mechanisms in a mouse myocardial infarction (MI) model. METHODS: The HDAC inhibitor trichostatin A (TSA, 0.1 mg/kg/day) was administered via daily intraperitoneal injections for 8 consecutive weeks after MI in C57/BL mice...
2018: Cellular Physiology and Biochemistry
Sandro Goruppi, Seung-Hee Jo, Csaba Laszlo, Andrea Clocchiatti, Victor Neel, G Paolo Dotto
Cancer-associated fibroblasts (CAFs) are important at all tumor stages. CSL/RBPJκ suppresses the gene expression program leading to CAF activation and associated metabolic reprogramming, as well as autophagy. Little is known about CSL protein turnover, especially in the tumor microenvironment. We report that, in human dermal fibroblasts (HDFs), conditions inducing autophagy-often found in tumor stroma-down-regulate CSL protein levels but do not affect its mRNA levels. Genetic or pharmacologic targeting of the autophagic machinery blocks CSL down-modulation...
September 18, 2018: Cell Reports
Weijie Wen, Jianwen Chen, Liugang Ding, Xia Luo, Xueping Zheng, Qi Dai, Qianqian Gu, Cui Liu, Ming Liang, Xiaolei Guo, Peiqing Liu, Min Li
BACKGROUND: Astragalus membranaceus is a fundamental herb in Traditional Chinese Medicine and has attracted significant attention due to its anti-inflammatory, and longevity effects. However, its anti-photoaging property remains to be defined. Autophagy plays important roles in regulating cell homeostasis and aging processes. Whether regulation of autophagy could be an efficient way for anti-photoaging is still unclear. OBJECTIVE: To investigate the effects and the possible mechanism of astragaloside on anti-photoaging in UVB-induced photoaging cell model...
September 14, 2018: Archives of Biochemistry and Biophysics
Valentina Basso, Elena Marchesan, Caterina Peggion, Joy Chakraborty, Sophia von Stockum, Marta Giacomello, Denis Ottolini, Valentina Debattisti, Federico Caicci, Elisabetta Tasca, Valentina Pegoraro, Corrado Angelini, Angelo Antonini, Alessandro Bertoli, Marisa Brini, Elena Ziviani
Parkin, an E3 ubiquitin ligase and a Parkinson's disease (PD) related gene, translocates to impaired mitochondria and drives their elimination via autophagy, a process known as mitophagy. Mitochondrial pro-fusion protein Mitofusins (Mfn1 and Mfn2) were found to be a target for Parkin mediated ubiquitination. Mfns are transmembrane GTPase embedded in the outer membrane of mitochondria, which are required on adjacent mitochondria to mediate fusion. In mammals, Mfn2 also forms complexes that are capable of tethering mitochondria to endoplasmic reticulum (ER), a structural feature essential for mitochondrial energy metabolism, calcium (Ca2+ ) transfer between the organelles and Ca2+ dependent cell death...
September 13, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Jia Liu, Xiaoxuan Wang, Ming Zheng, Qingxian Luan
AIMS: Lipopolysaccharide (LPS) is a major component of cell wall in gram-negative bacteria and has been proved to be a predominant pathogenic factor in periodontitis. Porphyromonas gingivalis (P.g) was abundant in patients with periodontitis and was associated with patient clinic-pathological characteristics. Furthermore, autophagy is a potential mechanism in inflammatory disease. In this study, we hypothesized that LPS from P.g may affect the physiological functions of human gingival fibroblasts (HGFs) through activating cellular autophagy...
October 15, 2018: Life Sciences
Seo-Yeon Park, Eun Jung Byun, Jeong Deuk Lee, Sungjoo Kim, Hei Sung Kim
A World Health Organization (WHO) report from 2016 states that over 3 million people die annually from air pollution, which places air pollution as the world's largest single environmental health risk factor. Particulate matter (PM) is one of the main components of air pollution, and there is increasing evidence that PM exposure exerts negative effects on the human skin. To see the impact of air pollution on skin aging, we analyzed the effect of PM exposure on human dermal fibroblasts (HDFs) with Western blot, enzyme-linked immunosorbent assay (ELISA), and gene analysis...
September 12, 2018: International Journal of Molecular Sciences
Winifred W Yau, Brijesh K Singh, Ronny Lesmana, Jin Zhou, Rohit A Sinha, Kiraely A Wong, Yajun Wu, Boon-Huat Bay, Shigeki Sugii, Lei Sun, Paul M Yen
The thyroid hormone triiodothyronine (T3 ) activates thermogenesis by uncoupling electron transport from ATP synthesis in brown adipose tissue (BAT) mitochondria. Although T3 can induce thermogenesis by sympathetic innervation, little is known about its cell autonomous effects on BAT mitochondria. We thus examined effects of T3 on mitochondrial activity, autophagy, and metabolism in primary brown adipocytes and BAT and found that T3 increased fatty acid oxidation and mitochondrial respiration as well as autophagic flux, mitophagy, and mitochondrial biogenesis...
September 13, 2018: Autophagy
Julia K Götzl, Alessio-Vittorio Colombo, Katrin Fellerer, Anika Reifschneider, Georg Werner, Sabina Tahirovic, Christian Haass, Anja Capell
BACKGROUND: Heterozygous loss-of-function mutations in the progranulin gene (GRN) lead to frontotemporal lobar degeneration (FTLD) while the complete loss of progranulin (PGRN) function results in neuronal ceroid lipofuscinosis (NCL), a lysosomal storage disease. Thus the growth factor-like protein PGRN may play an important role in lysosomal degradation. In line with a potential lysosomal function, PGRN is partially localized and processed in lysosomes. In the central nervous system (CNS), PGRN is like other lysosomal proteins highly expressed in microglia, further supporting an important role in protein degradation...
September 4, 2018: Molecular Neurodegeneration
Silvia Castagnaro, Martina Chrisam, Matilde Cescon, Paola Braghetta, Paolo Grumati, Paolo Bonaldo
Collagen VI (ColVI) is an abundant and distinctive extracellular matrix protein secreted by fibroblasts in different tissues. Human diseases linked to mutations on ColVI genes are primarily affecting skeletal muscle due to non-cell autonomous myofiber defects. To date, it is not known whether and how fibroblast homeostasis is affected by ColVI deficiency, a critical missing information as this may strengthen the use of patients' fibroblasts for preclinical purposes. Here, we established primary and immortalized fibroblast cultures from ColVI null ( Col6a1 -/- ) mice, the animal model of ColVI-related diseases...
2018: Frontiers in Physiology
Zhang Zhao, Guo-Chang Liu, Wen Fu
This study aims to explore the role of PERK-eIF2α signaling pathway in fetal male rats with hypospadias induced by maternal exposure to di-n-butyl phthalate (DBP). DBP was used to treat pregnant SD rats by gastric intubation from gestation day (GD) 14-18 to construct a hypospadias rat model. The amount, weight, anogenital distance (AGD), and hypospadias incidence of rats were recorded and the genital tubercle (GT) of fetal male rats was collected on GD 19. Western blotting was performed to detect the expressions of PERK-eIF2α pathway- and autophagy-related proteins, and cell apoptosis was detected using TUNEL method...
September 2018: Kaohsiung Journal of Medical Sciences
Philip Seibler, Lena F Burbulla, Marija Dulovic, Simone Zittel, Johanne Heine, Thomas Schmidt, Franziska Rudolph, Ana Westenberger, Aleksandar Rakovic, Alexander Münchau, Dimitri Krainc, Christine Klein
Beta-propeller protein-associated neurodegeneration is a subtype of monogenic neurodegeneration with brain iron accumulation caused by de novo mutations in WDR45. The WDR45 protein functions as a beta-propeller scaffold and plays a putative role in autophagy through its interaction with phospholipids and autophagy-related proteins. Loss of WDR45 function due to disease-causing mutations has been linked to defects in autophagic flux in patient and animal cells. However, the role of WDR45 in iron homeostasis remains elusive...
October 1, 2018: Brain: a Journal of Neurology
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