Emerging role for branched-chain amino acids metabolism in fibrosis

被引:25
作者
Wu, Tiangang [1 ]
Wang, Mengling [1 ]
Ning, Fengling [1 ]
Zhou, Shilin [1 ]
Hu, Xuetao [1 ]
Xin, Hong [1 ,3 ]
Reilly, Svetlana [2 ]
Zhang, Xuemei [1 ]
机构
[1] Fudan Univ, Sch Pharm, Dept Pharmacol, Shanghai 201203, Peoples R China
[2] Univ Oxford, John Radcliffe Hosp, British Heart Fdn Ctr Res Excellence, Radcliffe Dept Med,Div Cardiovasc Med, Oxford, England
[3] Shanghai Zhangjiang Inst Med Innovat, Shanghai 201204, Peoples R China
关键词
Fibrosis; Branched-chain amino acids; Metabolism; Liver; ALPHA-KETOACID DEHYDROGENASE; INTERSTITIAL FIBROBLAST ACTIVATION; EXTRACELLULAR-MATRIX; INSULIN-RESISTANCE; LIVER FIBROSIS; ISOENZYME PATTERNS; GAMMA EXPRESSION; TGF-BETA/SMAD; FATTY-ACID; KIDNEY;
D O I
10.1016/j.phrs.2022.106604
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Fibrosis is a common pathological feature of organ diseases resulting from excessive production of extracellular matrix, which accounts for significant morbidity and mortality. However, there is currently no effective treat-ment targeting fibrogenesis. Recently, metabolic alterations are increasingly considered as essential factors underlying fibrogenesis, and especially research on metabolic regulation of amino acids is flourishing. Among them, branched-chain amino acids (BCAAs) are the most abundant essential amino acids, including leucine, isoleucine and valine, which play significant roles in the substance and energy metabolism and their regulation. Dysregulation of BCAAs metabolism has been proven to contribute to numerous diseases. In this review, we summarize the metabolic regulation of fibrosis and the changes in BCAAs metabolism secondary to fibrosis. We also review the effects and mechanisms of the BCAAs intervention, and its therapeutic targeting in hepatic, renal and cardiac fibrosis, with a focus on the fibrosis in liver and associated hepatocellular carcinoma.
引用
收藏
页数:12
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共 147 条
[1]   The Role of Cancer-Associated Fibroblasts and Fibrosis in Liver Cancer [J].
Affo, Silvia ;
Yu, Le-Xing ;
Schwabe, Robert F. .
ANNUAL REVIEW OF PATHOLOGY: MECHANISMS OF DISEASE, VOL 12, 2017, 12 :153-186
[2]   Alteration in kidney glucose and amino acids are implicated in renal pathology in MRL/lpr mice [J].
Alexander, Jessy J. ;
Zwingmann, Claudia ;
Jacob, Alexander ;
Quigg, Richard .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2007, 1772 (10) :1143-1149
[3]   siRNA Knockdown of Tissue Inhibitor of Metalloproteinase-1 in Keloid Fibroblasts Leads to Degradation of Collagen Type I [J].
Aoki, Masayo ;
Miyake, Koichi ;
Ogawa, Rei ;
Dohi, Teruyuki ;
Akaishi, Satoshi ;
Hyakusoku, Hiko ;
Shimada, Takashi .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2014, 134 (03) :818-826
[4]   Branched Chain Amino Acids in Metabolic Disease [J].
Arany, Zoltan ;
Neinast, Michael .
CURRENT DIABETES REPORTS, 2018, 18 (10)
[5]   Liver fibrosis [J].
Aydin, M. Merve ;
Akcali, Kamil Can .
TURKISH JOURNAL OF GASTROENTEROLOGY, 2018, 29 (01) :14-21
[6]   Glutaminolysis Epigenetically Regulates Antiapoptotic Gene Expression in Idiopathic Pulmonary Fibrosis Fibroblasts [J].
Bai, Le ;
Bernard, Karen ;
Tang, Xuebo ;
Hu, Min ;
Horowitz, Jeffrey C. ;
Thannickal, Victor J. ;
Sanders, Yan Y. .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 2019, 60 (01) :49-57
[7]   Remodelling the extracellular matrix in development and disease [J].
Bonnans, Caroline ;
Chou, Jonathan ;
Werb, Zena .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2014, 15 (12) :786-801
[8]   Transforming Growth Factor-β Receptors and Smads: Regulatory Complexity and Functional Versatility [J].
Budi, Erine H. ;
Duan, Dana ;
Derynck, Rik .
TRENDS IN CELL BIOLOGY, 2017, 27 (09) :658-672
[9]   Insulin resistance: A metabolic pathway to chronic liver disease [J].
Bugianesi, E ;
McCullough, AJ ;
Marchesini, G .
HEPATOLOGY, 2005, 42 (05) :987-1000
[10]   PPARγ Links BMP2 and TGFβ1 Pathways in Vascular Smooth Muscle Cells, Regulating Cell Proliferation and Glucose Metabolism [J].
Calvier, Laurent ;
Chouvarine, Philippe ;
Legchenko, Ekaterina ;
Hoffmann, Nadine ;
Geldner, Jonas ;
Borchert, Paul ;
Jonigk, Danny ;
Mozes, Miklos M. ;
Hansmann, Georg .
CELL METABOLISM, 2017, 25 (05) :1118-+