Probiotics counteract the expression of hepatic profibrotic genes via the attenuation of TGF-β/SMAD signaling and autophagy in hepatic stellate cells

被引:21
作者
Kanmani, Paulraj [1 ,2 ]
Kim, Hojun [1 ]
机构
[1] Dongguk Univ, Dept Korean Med, Goyang, South Korea
[2] Univ Illinois, Dept Med, Chicago, IL USA
来源
PLOS ONE | 2022年 / 17卷 / 01期
基金
新加坡国家研究基金会;
关键词
LIVER FIBROSIS; BETA RECEPTOR; GROWTH; MICE; FIBROGENESIS; INFLAMMATION; DISEASE; MODEL;
D O I
10.1371/journal.pone.0262767
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Hepatic fibrosis is caused by the increased accumulation and improper degradation of extracellular matrix (ECM) proteins in the liver. Hepatic stellate cells (HSCs) activation is a key process in initiating hepatic fibrosis and can be ameliorated by the administration of probiotic strains. This study hypothesized that LAB strains (Lactiplantibacillus plantarum, Lactobacillus brevis, and Weissella cibaria) might attenuate pro-fibrogenic cytokine TGF-beta mediated HSCs activation and induce collagen deposition, expression of other fibrogenic/inflammatory markers, autophagy, and apoptotic processes in vitro. Few studies have evaluated the probiotic effects against fibrogenesis in vitro. In this study, TGF-beta exposure increased collagen deposition in LX-2 cells, but this increase was diminished when the cells were pretreated with LAB strains before TGF-beta stimulation. TGF-beta not only increased collagen deposition, but it also significantly upregulated the mRNA levels of Coll Al , alpha-smooth muscle actin (alpha-SMA), matrix metalloproteinases-2 (MMP-2), IL-6, CXCL-8, CCL2, and IL-1 beta in LX-2 cells. Pretreatment of the cells with LAB strains counteracted the TGF-beta-induced pro-fibrogenic and inflammatory markers by modulating SMAD-dependent and SMAD-independent TGF-beta signaling. In addition, LX-2 cells exposed to TGF-beta induced the autophagic and apoptotic associated proteins that were also positively regulated by the LAB strains. These findings suggest that LAB can attenuate TGF-beta signaling that is associated with liver fibrogenesis.
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页数:18
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共 42 条
  • [21] A practical clinical approach to liver fibrosis
    Kumar, Rahul
    Teo, Eng Kiong
    How, How Choon
    Wong, Teck Yee
    Ang, Tiing Leong
    [J]. SINGAPORE MEDICAL JOURNAL, 2018, 59 (12) : 628 - 632
  • [22] Autophagy modulation in bladder cancer development and treatment
    Li, Faping
    Guo, Hui
    Yang, Yuxuan
    Feng, Mingliang
    Liu, Bin
    Ren, Xiang
    Zhou, Honglan
    [J]. ONCOLOGY REPORTS, 2019, 42 (05) : 1647 - 1655
  • [23] Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice
    Li, Jun
    Sung, Cecilia Ying Ju
    Lee, Nikki
    Ni, Yueqiong
    Pihlajamaki, Jussi
    Panagiotou, Gianni
    El-Nezami, Hani
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2016, 113 (09) : E1306 - E1315
  • [24] Transcriptional Repression of the Transforming Growth Factor β (TGF-β) Pseudoreceptor BMP and Activin Membrane-bound Inhibitor (BAMBI) by Nuclear Factor κB (NF-κB) p50 Enhances TGF-β Signaling in Hepatic Stellate Cells
    Liu, Cheng
    Chen, Xiaorong
    Yang, Ling
    Kisseleva, Tatiana
    Brenner, David A.
    Seki, Ekihiro
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (10) : 7082 - 7091
  • [25] Non-Smad TGF-β signals
    Moustakas, A
    Heldin, CH
    [J]. JOURNAL OF CELL SCIENCE, 2005, 118 (16) : 3573 - 3584
  • [26] (-)-Catechin-7-O-β-d-Apiofuranoside Inhibits Hepatic Stellate Cell Activation by Suppressing the STAT3 Signaling Pathway
    Park, Yong Joo
    Kim, Dong Min
    Jeong, Mi Ho
    Yu, Jae Sik
    So, Hae Min
    Bang, In Jae
    Kim, Ha Ryong
    Kwon, Seung-Hwan
    Kim, Ki Hyun
    Chung, Kyu Hyuck
    [J]. CELLS, 2020, 9 (01)
  • [27] TLR4 enhances TGF-β signaling and hepatic fibrosis
    Seki, Ekihiro
    De Minicis, Samuele
    Oesterreicher, Christoph H.
    Kluwe, Johannes
    Osawa, Yosuke
    Brenner, David A.
    Schwabe, Robert F.
    [J]. NATURE MEDICINE, 2007, 13 (11) : 1324 - 1332
  • [28] Autophagy in health and disease: A double-edged sword
    Shintani, T
    Klionsky, DJ
    [J]. SCIENCE, 2004, 306 (5698) : 990 - 995
  • [29] An open-label, randomized, placebo-controlled study on the effectiveness of a novel probiotics administration protocol (ProbiotiCKD) in patients with mild renal insufficiency (stage 3a of CKD)
    Simeoni, Mariadelina
    Citraro, Maria Lucia
    Cerantonio, Annamaria
    Deodato, Francesca
    Provenzano, Michele
    Cianfrone, Paola
    Capria, Maria
    Corrado, Silvia
    Libri, Emanuela
    Comi, Alessandro
    Pujia, Arturo
    Abenavoli, Ludovico
    Andreucci, Michele
    Cocchi, Massimo
    Montalcini, Tiziana
    Fuiano, Giorgio
    [J]. EUROPEAN JOURNAL OF NUTRITION, 2019, 58 (05) : 2145 - 2156
  • [30] Pretreatment with probiotic Bifico ameliorates colitis-associated cancer in mice: Transcriptome and gut flora profiling
    Song, Huan
    Wang, Weiyi
    Shen, Bo
    Jia, Hao
    Hou, Zhaoyuan
    Chen, Ping
    Sun, Yunwei
    [J]. CANCER SCIENCE, 2018, 109 (03): : 666 - 677