Interleukin-22 ameliorates liver fibrosis through miR-200a/beta-catenin.
IL-22 ameliorates liver fibrosis by inhibiting hepatic stellate cells (HSC), and loss of miR-200a is associated with the development of liver fibrosis. The study aimed to investigate the interplay between IL-22 and miR-200a in regulating liver fibrosis in vivo and in vitro. We observed that IL-22 significantly reduced the proliferation of HSC and increased the expression of p-STAT3. β-catenin was identified as a target gene of miR-200a by luciferase reporter assay, and upregulation of miR-200a significantly attenuated the proliferation of HSC and reduced β-catenin expression. IL-22 treatment increased expression of miR-200a and decreased expression of β-catenin in HSC. The expression of p-STAT3 and miR-200a was elevated while β-catenin was decreased in fibrotic rat liver after IL-22 treatment. Expression levels of β-catenin and p-STAT3 were inversely correlated in fibrotic rat liver and HSC. Upregulation of β-catenin suppressed expression of p-STAT3 in HSC. We concluded that IL-22 inhibits HSC activation and ameliorates liver fibrosis through enhancing expression of miR-200a and reducing expression of β-catenin, suggesting there may be a crosstalk between IL-22/STAT3 and β-catenin pathway.
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Bang-Li
BL
Hu
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Cheng
C
Shi
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Rong-E
RE
Lei
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Dong-Hong
DH
Lu
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Wei
W
Luo
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Shan-Yu
SY
Qin
Systems Immunity University Research Institute, Cardiff University School of Medicine, Heath Park, Cardiff, UK.
You
Y
Zhou
Department of Gastroenterology, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China.
Hai-Xing
HX
Jiang
D000199:Actins / Q000032:analysis; D000818:Animals; D000070416:Antagomirs / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D051186:Armadillo Domain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000032:analysis; D055166:Hepatic Stellate Cells / Q000166:cytology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D050796:STAT3 Transcription Factor / Q000378:metabolism; D016415:Sequence Alignment; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D000097043:Interleukin-22
D000199:Actins; D000070416:Antagomirs; D051186:Armadillo Domain Proteins; D024042:Collagen Type I; D007378:Interleukins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D053773:Transforming Growth Factor beta1; D000097043:Interleukin-22; C484654:Ctnnd2 protein, rat; C533896:MIRN200 microRNA, human; C498862:Acta2 protein, rat