title: Glutamine inhibits CCl4 induced liver fibrosis in mice and TGF-β1 mediated epithelial-mesenchymal transition in mouse hepatocytes.
abstract: Glutamine, traditionally a non-essential amino acid, now has been considered as essential in serious illness and injury. It is a major precursor for glutathione synthesis. However, the anti-fibrotic effect of glutamine and its molecular mechanism in experimental liver fibrosis have not been explored. In the present study we aimed to examine the potential role of glutamine in carbon tetrachloride (CCl4) induced liver fibrosis and TGF-β1 mediated epithelial mesenchymal transition (EMT) and apoptosis in mouse hepatocytes. Liver fibrosis was induced by intraperitoneal injection of CCl4 three times a week for 10 weeks. Glutamine treatment effectively attenuated liver injury and oxidative stress. Collagen content was significantly decreased in liver sections of glutamine treated mice compared to CCl4 model mice. Furthermore, glutamine decreased expression level of α-SMA and TGF-β in liver tissue. Our in vitro study showed that TGF-β1 treatment in hepatocytes resulted in loss of E-cadherin and increased expression of mesenchymal markers and EMT related transcription factor. In addition, TGF-β1 increased the expression of apoptotic markers. However, glutamine interestingly suppressed TGF-β1 mediated EMT and apoptosis. In conclusion, our results suggest that glutamine ameliorates CCl4 induced liver fibrosis and suppresses TGF-β1 induced EMT progression and apoptosis.
authors.affiliation: Laboratory of Liver Regeneration, Biomedical Research Institute, Chonbuk National University Hospital, 561-712, Jeonju, South Korea.
authors.forename: Nirajan
authors.initials: N
authors.lastname: Shrestha
authors.affiliation: Laboratory of Liver Regeneration, Biomedical Research Institute, Chonbuk National University Hospital, 561-712, Jeonju, South Korea.
authors.forename: Lokendra
authors.initials: L
authors.lastname: Chand
authors.affiliation: Department of Microbiology, Chonbuk National University Medical School, 561-712, Jeonju, South Korea.
authors.forename: Myung Kwan
authors.initials: MK
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, 561-712, Jeonju, South Korea.
authors.forename: Seung Ok
authors.initials: SO
authors.lastname: Lee
authors.affiliation: Department of Surgery, Chonbuk National University Medical School, 561-712, Jeonju, South Korea.
authors.forename: Chan Young
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Laboratory of Liver Regeneration, Biomedical Research Institute, Chonbuk National University Hospital, 561-712, Jeonju, South Korea; Department of Surgery, Chonbuk National University Medical School, 561-712, Jeonju, South Korea. Electronic address: surgeon@jbnu.ac.kr.
authors.forename: Yeon Jun
authors.initials: YJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002251:Carbon Tetrachloride / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D005434:Flow Cytometry; D005973:Glutamine / Q000494:pharmacology*; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D005973:Glutamine; D002251:Carbon Tetrachloride
keywords: Carbon tetrachloride; Epithelial–mesenchymal transition; Glutamine; Liver fibrosis; Oxidative stress; Transforming growth factor-β