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Fibroblast autophagy

Yasuomi Urano, Chinatsu Mori, Ayano Fuji, Keito Konno, Takayuki Yamamoto, Shohei Yashirogi, Mayu Ando, Yoshiro Saito, Noriko Noguchi
PARK7/DJ-1 is a Parkinson disease- and cancer-associated protein that functions as a multifunctional protein involved in gene transcription regulation and anti-oxidative defense. Although PARK7 lacks the secretory signal sequence, it is secreted and plays important physiological and pathophysiological roles. Whereas secretory proteins that lack the endoplasmic reticulum-targeting signal sequence are secreted from cells by way of what is called the unconventional secretion mechanism, the specific processes responsible for causing PARK7 to be secreted across the plasma membrane have remained unclear...
August 16, 2018: Autophagy
María Inés Molejon, Mirna Swayden, Daniele Fanale, Jennifer Bintz, Odile Gayet, Philippe Soubeyran, Juan Iovanna
In this study, our aim is to assess the role played by autophagy and its inhibition in the different PDAC cellular compartments, and its involvement in chemo-resistance using primary human pancreatic cancer-derived cells (PCC) and Cancer Associated Fibroblasts (CAF). Autophagy flux, as measured by LC3-I and -II in the presence of Chloroquine, showed a variable level in PCC and CAFs. We found no correlation between autophagy level and degree of tumor differentiation. Association of Chloroquine with gemcitabine, 5FU, oxaliplatin, irinotecan and docetaxel revealed that its effect on survival is cell- and drug-dependent in vitro and in vivo ...
July 20, 2018: Oncotarget
Koji Osuka, Yasuo Watanabe, Nobuteru Usuda, Masahiro Aoyama, Mikinobu Takeuchi, Masakazu Takayasu
Chronic subdural hematoma (CSDH) is fundamentally treatable, although it sometimes recurs. We observed, however, several cases of spontaneous resolution of CSDH outer membranes, even in a trabecular type of CSDH, after a trepanation surgical procedure. In this study, we examined the expression of molecules of the autophagy signaling pathway in CSDH outer membranes. Eight patients whose outer membranes were obtained successfully during trepanation were included in this study. By Western blot analysis, we examined the expression of mammalian target of rapamycin (mTOR); GβL; UNC-51-like kinase-1 (ULK1); Beclin-1; autophagy-related genes (Atg) 3, 5, 7, 12, 13, and 16L1β,α; the autophagy marker Light Chain3A/B (LC3A/B); and β-actin, which constitute the autophagy signaling pathway...
August 14, 2018: Journal of Neurotrauma
Eirini Vasarmidi, Stella Sarantoulaki, Athina Trachalaki, George Margaritopoulos, Eleni Bibaki, Demetrios A Spandidos, Nikolaos Tzanakis, Katerina Antoniou
Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease with a poor prognosis and limited therapeutic options. Over the past decade, research efforts have focused on the pathogenetic mechanisms involved in this enigmatic lung disease. Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease often complicated by the development of interstitial lung disease (ILD), leading to high mortality and morbidity. Autophagy is a process regulating the turnover of subcellular components and organelles, and represents a major cellular homeostatic mechanism...
August 6, 2018: Molecular Medicine Reports
Jihong Shi, Houan Xiao, Jun Li, Julei Zhang, Yan Li, Jian Zhang, Xujie Wang, Xiaozhi Bai, Ke Tao, Dahai Hu, Hao Guan
Hypertrophic scarring is a serious fibrotic skin disease, and the abnormal activation of hypertrophic scar fibroblasts (HSFs) intensifies its pathogenesis. Our previous studies have demonstrated that the dysregulation of autophagy in HSFs is associated with fibrosis. However, knowledge regarding the regulation of HS fibrosis by p53-modulated autophagy is limited. Here, we investigated the effect of p53-modulated autophagy on HS fibrosis. The overexpression of wtp53 (Adp53) promoted autophagic capacity and inhibited collagen and α-SMA expression in HSFs...
August 8, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
De Li, Chenglong Wang, Zhuokai Li, Hui Wang, Jiye He, Junfeng Zhu, Yuehui Zhang, Chao Shen, Fei Xiao, Yuan Gao, Xiang Zhang, Yang Li, Peng Wang, Jianping Peng, Guiquan Cai, Bin Zuo, Yuehua Yang, Yun Shen, Weidong Song, Xiaoling Zhang, Lei Shen, Xiaodong Chen
Aseptic loosening is mainly caused by wear debris generated by friction that can increase the expression of receptor activation of nuclear factor (NF)-κB (RANKL). RANKL has been shown to support the differentiation and maturation of osteoclasts. Although autophagy is a key metabolic pathway for maintaining the metabolic homeostasis of cells, no study has determined whether autophagy induced by Al2 O3 particles is involved in the pathogenesis of aseptic loosening. The aim of this study was to evaluate RANKL levels in patients experiencing aseptic loosening after total hip arthroplasty (THA) and hip osteoarthritis (hOA) and to consequently clarify the relationship between RANKL and LC3II expression...
August 6, 2018: Cell Death & Disease
Haichang Yin, Lili Zhao, Yiping Wang, Siqi Li, Hong Huo, Hongyan Chen
BACKGROUND: The results of our previous study showed that impaired cellular energy metabolism contributes to duck enteritis virus-induced autophagy via the 5`-adenosine monophosphate-activated protein kinase (AMPK)/tuberous sclerosis complex 2/mammalian target of rapamycin pathway in duck embryo fibroblast (DEF) cells. However, it remains unknown whether any other underlying mechanisms of AMPK activation are involved in autophagy induction. METHODS: The activity of CaMKKβ and AMPK in DEF cells infected with DEV were evaluated...
August 6, 2018: Virology Journal
Hei Sung Kim, Seo-Yeon Park, Seok Hoon Moon, Jeong Deuk Lee, Sungjoo Kim
Autophagy is an intracellular stress response that is enhanced under starvation conditions, and also when the cellular components are damaged. Aging accompanies an increase in intracellular stress and has significant impact on the skin. Since dermal fibroblasts are a powerful indicator of skin aging, we compared the autophagic activity of human skin fibroblasts between the young and old. According to TEM analyses, the number of autophagosomes per 1 μm² cytoplasmic area was similar between young and aged fibroblasts...
August 1, 2018: International Journal of Molecular Sciences
Jianbin Zhang, Jigang Wang, Zhihong Zhou, Jung-Eun Park, Liming Wang, Shuai Wu, Xin Sun, Liqin Lu, Tianru Wang, Qingsong Lin, Siu Kwan Sze, Dongsheng Huang, Han-Ming Shen
TFEB (transcription factor EB) is a master regulator of lysosomal biogenesis, function and autophagy. The transcriptional activity of TFEB is mainly controlled by its phosphorylation status mediated by the MTOR (mechanistic target of rapamycin [serine/threonine kinase]) complex 1 (MTORC1). At present, little is known whether other forms of posttranslational modifications (PTMs) such as acetylation also affects is transcriptional activity. In this study, we first observed that a well-established histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) activated lysosomal function in human cancer cells, a process independent of the MTORC1 pathway...
July 30, 2018: Autophagy
Chiharu Graybill, Michael J Morgan, Myron J Levin, Katherine S Lee
Macroautophagy (herein referred to as autophagy) is a lysosomal degradation mechanism that is important for maintaining homeostasis and for coping with cellular stress such as nutrient deprivation. Previously, varicella-zoster virus (VZV) was reported to modulate the autophagy pathway in the host. However, how VZV affects the autophagy pathway is still unclear. In this study, we examined how wild-type rOka and attenuated vOka strains of cell-associated VZV affect autophagy in MRC-5 fibroblasts by using ratiometric flow cytometry and immunoblotting methods...
September 2018: Virology
Yue Zhou, Thiam Chien Shiok, Arthur Mark Richards, Peipei Wang
AIMS: MiR-101a is reported to reduce post-infarction myocardial fibrosis through targeting c-FOS and TGFbr1. However the actions of miR-101a within the TGF-β signaling pathway are largely unknown. We demonstrate the mechanisms underlying mutual inhibition between miR-101a and TGF-β signaling and explore the therapeutic potential of miR-101a in suppressing pressure overload-induced cardiac fibrosis. METHODS AND RESULTS: The effects of miR-101a on fibroblast proliferation, myofibroblast transdifferentiation, collagen synthesis, apoptosis, and autophagy were assessed in isolated rat cardiac fibroblasts (cFB)...
July 24, 2018: Journal of Molecular and Cellular Cardiology
Haibing Wang, Xue Yang, Qianqian Yang, Lingling Gong, Hao Xu, Zonggui Wu
Post-MI heart failure is characterized by structural remodeling, in which intramyocardial fibrosis takes a important part. Poly(ADP-ribose) polymerase 1 (PARP-1) is a extensive nuclear enzyme and plays a critical role in various diseases. It was shown that PARP-1 inhibition could alleviate heart failure and dowregulate autophagy, but whether PARP-1 regulates autophagy and thus impacts the activities of CFs remain unknown. We transfected cultured cardiac fibroblasts (CFs) with small interfere RNA-PARP-1 (siPARP-1) to downregulate PARP-1 and analyzed the ability of proliferation, migration, differentiation, and autophagy levels of CFs under different treatments using CCK8 assays, transwell migration assays, immunofluorescence assays detecting expression of α-SMA, western blot assays detecting autophagy-related proteins respectively...
July 21, 2018: Biochemical and Biophysical Research Communications
Zsófia Ulakcsai, Fruzsina Bagaméry, Éva Szökő, Tamás Tábi
We aimed at studying the potential mechanisms in the preventive effect of resveratrol on serum deprivation induced caspase 3 activation on non-transformed cells. METHODS: Apoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation, reactive oxygen species production and depolarization of the mitochondrial membrane were measured by fluorescence methods. The involvement of intracellular receptors and autophagy in the effect of resveratrol were analyzed by using specific agonists and antagonists...
July 20, 2018: European Journal of Pharmaceutical Sciences
Sokhna M S Yakhine-Diop, Mireia Niso-Santano, Mario Rodríguez-Arribas, Rubén Gómez-Sánchez, Guadalupe Martínez-Chacón, Elisabet Uribe-Carretero, José A Navarro-García, Gema Ruiz-Hurtado, Ana Aiastui, J Mark Cooper, Adolfo López de Munaín, José M Bravo-San Pedro, Rosa A González-Polo, José M Fuentes
Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder. While most PD cases are idiopathic, the known genetic causes of PD are useful to understand common disease mechanisms. Recent data suggests that autophagy is regulated by protein acetylation mediated by histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities. The changes in histone acetylation reported to be involved in PD pathogenesis have prompted this investigation of protein acetylation and HAT and HDAC activities in both idiopathic PD and G2019S leucine-rich repeat kinase 2 (LRRK2) cell cultures...
July 21, 2018: Molecular Neurobiology
Thomas Nury, Randa Sghaier, Amira Zarrouk, Franck Ménétrier, Tugba Uzun, Valerio Leoni, Claudio Caccia, Wiem Meddeb, Amira Namsi, Khouloud Sassi, Wafa Mihoubi, Jean-Marc Riedinger, Mustapha Cherkaoui-Malki, Thibault Moreau, Anne Vejux, Gérard Lizard
The involvement of organelles in cell death is well established especially for endoplasmic reticulum, lysosomes and mitochondria. However, the role of the peroxisome is not well known, though peroxisomal dysfunction favors a rupture of redox equilibrium. To study the role of peroxisomes in cell death, 158 N murine oligodendrocytes were treated with 7-ketocholesterol (7 KC: 25-50 μM, 24 h). The highest concentration is known to induce oxiapoptophagy (OXIdative stress + APOPTOsis + autoPHAGY), whereas the lowest concentration does not induce cell death...
July 19, 2018: Biochimie
Ao Feng, Chen Ling, Lin Xin-Duo, Wu Bing, Wu San-Wu, Zhan Yu, Huang Yu-Lan, Zhang You-En
Autophagy, an intracellular bulk degradation process of proteins and organelles, can be induced by myocardial ischemia in the heart. However, the causative role of autophagy in the survival of human cardiac fibroblasts and the underlying mechanisms are incompletely understood. Oxidative stress can induce autophagy in cultured cells upon hydrogen peroxide (H2 O2 ) exposure. Because hydrogen sulfide (H2 S) regulates reactive oxygen species (ROS) and apoptosis, we hypothesize that H2 S may have a cardioprotective function...
August 2018: Cell Transplantation
Rongjie Lin, Zizhuo Su, Xiaohui Tan, Yinqing Su, Yuyang Chen, Xiaorong Shu, Shumin Liang, Jingfeng Wang, Shuanglun Xie
BACKGROUND: Acute myocardial infarction (AMI) is reported to be accompanied by endoplasmic reticulum (ER) stress and autophagy induction. Nevertheless, the roles of ER stress and autophagy in post-infarct reparative fibrosis remain to be elucidated. AIM: To investigate the effects of ER stress and autophagy on the regulation of post-infarct reparative fibrosis. METHODS: The expression of GRP78 and LC3 in cardiac fibroblasts in human heart tissues obtained from patients with or without AMI was assessed by immunofluorescence...
July 12, 2018: Archives of Medical Research
Alessandro Agnarelli, Marco Natali, Mercedes Garcia-Gil, Rossana Pesi, Maria Grazia Tozzi, Chiara Ippolito, Nunzia Bernardini, Robert Vignali, Renata Batistoni, Anna Maria Bianucci, Silvia Marracci
The natural alkaloid berberine has several pharmacological properties and recently received attention as a potential anticancer agent. In this work, we investigated the molecular mechanisms underlying the anti-tumor effect of berberine on glioblastoma U343 and pancreatic carcinoma MIA PaCa-2 cells. Human dermal fibroblasts (HDF) were used as non-cancer cells. We show that berberine differentially affects cell viability, displaying a higher cytotoxicity on the two cancer cell lines than on HDF. Berberine also affects cell cycle progression, senescence, caspase-3 activity, autophagy and migration in a cell-specific manner...
July 13, 2018: Scientific Reports
Long Yuan, Fan Zhang, Xiaowei Qi, Yongjun Yang, Chang Yan, Jun Jiang, Jun Deng
BACKGROUND: Autophagy regulation through exogenous materials has aroused intensive attention to develop treatment protocols according to diverse human diseases. However, to the best of our knowledge, few examples have been reported to selectively control autophagy process and ultimately achieve efficient therapeutic potential. RESULTS: In this study, monolayers of poly (acryloyl-L, D and racemic valine) (L-PAV-AuNPs, D-PAV-AuNPs and L/D-PAV-AuNPs) chiral molecules were anchored on the surfaces of gold nanoparticles (PAV-AuNPs), and the subsequent chirality-selective effects on autophagy activation were thoroughly studied...
July 11, 2018: Journal of Nanobiotechnology
Yiming Zhang, Cassandra B Higgins, Allyson L Mayer, Indira U Mysorekar, Babak B Razani, Mark J Graham, Paul W Hruz, Brian J DeBosch
The macroautophagy/autophagy-inducing disaccharide, trehalose, has been proposed to be a promising therapeutic agent against neurodegenerative and cardiometabolic diseases. We recently showed that trehalose attenuates hepatic steatosis in part by blocking hepatocyte glucose transport to induce hepatocyte autophagic flux. However, although every major demonstration of trehalose action invokes activating autophagic flux as its primary function, the mechanism of action of trehalose in whole-body energy metabolism remains poorly defined...
July 12, 2018: Autophagy
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