title: Tumor Necrosis Factor-Like Weak Inducer of Apoptosis Promotes Hepatic Stellate Cells Migration via Canonical NF-κB/MMP9 Pathway.
abstract: In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) have mainly been assessed in association with liver regeneration. However, the effects of TWEAK on liver fibrosis have not been fully elucidated. To investigate the effects of TWEAK on human hepatic stellate cells (HSCs) and to explore the relevant potential mechanisms, human HSCs line-LX-2 were cultured with TWEAK. Cell migration was detected by transwell assay; cell viability was evaluated by Cell Counting Kit-8; the expression of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 gene was identified by quantitative real-time polymerase chain reaction and western blotting; the activity of matrix metalloproteinases (MMPs) was tested by enzyme-linked immuno sorbent assay; small interfering RNA transfection was applied for depletion of MMP9 and p65. The result of transwell assay revealed that TWEAK promoted LX-2 migration. Subsequently, our data testified that the expression and activity of MMP9 was induced by TWEAK in LX-2 cells, which enhanced the migration. Furthermore, our findings showed that TWEAK upregulated the phosphorylation of IκBα and p65 protein to increase MMP9 expression in LX-2 cells. Meanwhile, the alpha-smooth muscle actin, vimentin and desmin expression were upregulated following TWEAK treatment. The results in the present study revealed that TWEAK promotes HSCs migration via canonical NF-κB/MMP9 pathway, which possibly provides a molecular basis targeting TWEAK for the therapy of liver fibrosis.
authors.affiliation: Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Mingcui
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Aixiu
authors.initials: A
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Min
authors.initials: M
authors.lastname: Su
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Gastroenterology, Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, Jiangsu, China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Affiliated Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing, Jiangsu, China.
authors.forename: Yuzheng
authors.initials: Y
authors.lastname: Zhuge
mesh_terms: D002460:Cell Line; D002465:Cell Movement / Q000235:genetics*; D000074049:Cytokine TWEAK; D015972:Gene Expression Regulation, Neoplastic; D055166:Hepatic Stellate Cells / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D000072000:NF-KappaB Inhibitor alpha / Q000096:biosynthesis; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction / Q000235:genetics; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000378:metabolism*
chemical_list: D000074049:Cytokine TWEAK; D016328:NF-kappa B; C498143:RELA protein, human; C109743:TNFSF12 protein, human; D051996:Transcription Factor RelA; D048069:Tumor Necrosis Factors; D000072000:NF-KappaB Inhibitor alpha; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9