In Pancreatic Cancer PatientsL-Carnitine Supplementation in Pancreatic Cancer PatientsConclusions and Advices
In Pancreatic Cancer PatientsL-Carnitine Supplementation in Pancreatic Cancer PatientsConclusions and Advices for Daily PracticeAcknowledgementDisclosure StatementGastrointest Tumors 2015;two:19502 DOI: ten.1159/000442873 2016 S. Karger AG, Basel karger.com/gatG tner et al.: Nutrition in Pancreatic Cancer: A Overview
Sato et al. Respiratory Research (2016) 17:107 DOI ten.1186/s12931-016-0420-xRESEARCHOpen AccessMetformin attenuates lung fibrosis development by means of NOX4 suppressionNahoko Sato1,2, Naoki Takasaka1, Masahiro Yoshida1, Kazuya Tsubouchi1,3, Shunsuke Minagawa1, Jun Araya1, Nayuta Saito1, Yu Fujita1, Yusuke Kurita1, Kenji Kobayashi1, Saburo Ito1, Hiromichi Hara1, Tsukasa Kadota1, Haruhiko Yanagisawa1, Mitsuo Hashimoto1, Hirofumi Utsumi1, Hiroshi Wakui1, Jun Kojima1, Takanori Numata1, Yumi Kaneko1, Makoto Odaka4, Toshiaki Morikawa4, Katsutoshi Nakayama1, Hirotsugu Kohrogi2 and Kazuyoshi KuwanoAbstractBackground: Accumulation of profibrotic myofibroblasts in fibroblastic foci (FF) is a essential method for improvement of fibrosis throughout idiopathic pulmonary fibrosis (IPF) pathogenesis, and transforming growth factor (TGF)- plays a crucial regulatory function in OSM Protein Storage & Stability myofibroblast differentiation. Reactive oxygen species (ROS) has been proposed to be involved in the mechanism for TGF–induced myofibroblast differentiation. Metformin is often a biguanide antidiabetic medication and its pharmacological action is mediated through the activation of AMP-activated protein kinase (AMPK), which regulates not just energy homeostasis but also strain responses, including ROS. Therefore, we sought to investigate the inhibitory role of metformin in lung fibrosis development through modulating TGF- signaling. Procedures: TGF–induced myofibroblast differentiation in lung fibroblasts (LF) was made use of for in vitro models. The antifibrotic function of metfromin was examined within a Bleomycin (BLM)-induced lung fibrosis model. Final results: We located that TGF–induced myofibroblast differentiation was clearly inhibited by metformin GAS6 Protein Synonyms treatment in LF. Metformin-mediated activation of AMPK was responsible for inhibiting TGF–induced NOX4 expression. NOX4 knockdown and N-acetylcysteine (NAC) remedy illustrated that NOX4-derived ROS generation was vital for TGF-induced SMAD phosphorylation and myofibroblast differentiation. BLM remedy induced improvement of lung fibrosis with concomitantly enhanced NOX4 expression and SMAD phosphorylation, which was efficiently inhibited by metformin. Enhanced NOX4 expression levels have been also observed in FF of IPF lungs and LF isolated from IPF individuals. Conclusions: These findings recommend that metformin is usually a promising anti-fibrotic modality of treatment for IPF affected by TGF-. Keyword phrases: IPF, Metformin, NOX4, ROS, TGF- Abbreviations: AEC, Alveolar epithelial cells; AMPK, AMP-activated protein kinase; BALF, Bronchoalveolar lavage fluid; BLM, Bleomycin; BW, Body weight; CM-H2DCFDA, Chloromethyl derivative of 2′, 7′-dichlorodihydrofluorescein diacetate; DCF, 2′, 7′-Dichlorodihydrofluorescein; DMEM, Dulbecco’s Modified Eagle’s Medium; ECM, Extracellular matrix; FF, Fibroblastic foci; HE staining, Hematoxylin-Eosin staining; IPF, Idiopathic pulmonary fibrosis; LF, Lung fibroblasts; LPS, Lipopolysaccharide; MAP kinase, Mitogen activated protein kinase; NAC, N-acetylcysteine; NOX, NADPH oxidase; PI3K, Phosphoinositide 3-kinase; ROS, Reactive oxygen species; SEM, Common error on the mean; siRNA, Little interfering RNA; TGF-, Transforming development factor-; WB, Wester.
