title: Loss of Raf kinase inhibitor protein is associated with malignant progression in hepatic fibrosis.
abstract: Raf kinase inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. But its role in hepatic fibrogenesis remains unclear. In the present study, we found that the absence of RKIP expression significantly enhanced the proliferation of HSC-T6 cells. Reduced RKIP expression promoted the activation of HSCs and the accumulation of collagen, as evidenced by the increases in the levels of collagen I and α-smooth muscle actin. Moreover, down-regulating RKIP expression led to severe histopathological changes and collagen accumulation in hepatic tissues of rats with liver fibrosis. Furthermore, the absence of RKIP promoted the activation of ERK/MAPK pathway in vitro and in vivo. Our findings clearly demonstrate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. Loss of RKIP may be associated with malignant progression in hepatic fibrosis.
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China.
authors.forename: Quanfang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Wei
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Liang
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Nie
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Shengjuan
authors.initials: S
authors.lastname: Lu
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Chunyuan
authors.initials: C
authors.lastname: Lu
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Shimei
authors.initials: S
authors.lastname: Tan
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Shujuan
authors.initials: S
authors.lastname: Lv
authors.affiliation: Guangxi Medical University, Nanning 530021, China.
authors.forename: Lang
authors.initials: L
authors.lastname: Zhuo
authors.affiliation: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, China; Department of Biochemistry, University of Arkansas Medical School, 4301W. Markham, Little Rock, AR 72205-7199, USA.
authors.forename: Zhongpeng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Guangxi Medical University, Nanning 530021, China. Electronic address: gxLx60@163.com.
authors.forename: Xing
authors.initials: X
authors.lastname: Lin
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D049488:Phosphatidylethanolamine Binding Protein / Q000172:deficiency* / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D000199:Actins; D024042:Collagen Type I; D049488:Phosphatidylethanolamine Binding Protein; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D020782:Matrix Metalloproteinases
keywords: Collagen; Erk/mapk; Hepatic fibrosis; Proliferation; RKIP