title: Involvement of prolyl isomerase PIN1 in the cell cycle progression and proliferation of hepatic oval cells.
abstract: Liver regenerates remarkably after toxic injury or surgical resection. In the case of failure of resident hepatocytes to restore loss, repopulation is carried out by induction, proliferation, and differentiation of the progenitor cell. Although, some signaling pathways have been verified to contribute oval cell-mediated liver regeneration, role of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1(Pin1) in the oval cells proliferation is unknown. In the present study, we evaluate the role of Pin1 in oval cells proliferation. In our study, the expression of Pin1 in the mice liver increased after three weeks feeding of 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) diet along with the proliferation of oval cells. The expression of Pin1 was higher in oval cells compared to the hepatocytes.Pin1 inhibition by Juglone reduced oval cell proliferation, which was restored to normal when oval cells were treated with IGF-1. Consistent with increased cell growth, expression of Pin1, β-catenin and PCNA were increased in IGF-1 treated cells in a time dependent manner. In FACS analysis, siRNA-mediated knockdown of the Pin1 protein in the oval cells significantly increased the numbers of cells in G0/G1 phase. Furthermore, hepatocyte when treated with TGF-β showed marked reduction in cell proliferation and expression of Pin1 whereas this effect was not seen in the oval cells treated with TGF-β. In conclusion, Pin1 plays important role in the cell cycle progression and increase oval cells proliferation which may be crucial in chronic liver injury.
authors.affiliation: Laboratory of Liver Regeneration, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Geuman-dong, Duckjin-gu, Jeonju, 561-712, South Korea; Department of Biochemistry, School of Medical Sciences, Kathmandu University, Dhulikhel, Kavre, Nepal.
authors.forename: Prabodh
authors.initials: P
authors.lastname: Risal
authors.affiliation: Laboratory of Liver Regeneration, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Geuman-dong, Duckjin-gu, Jeonju, 561-712, South Korea.
authors.forename: Nirajan
authors.initials: N
authors.lastname: Shrestha
authors.affiliation: Laboratory of Liver Regeneration, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Geuman-dong, Duckjin-gu, Jeonju, 561-712, South Korea.
authors.forename: Lokendra
authors.initials: L
authors.lastname: Chand
authors.affiliation: Department of Surgery, Division of Pediatric Surgery, Stanford University School of Medicine, PSRL, 257 Campus Drive, Stanford, CA 94305-5148, USA.
authors.forename: Karl G
authors.initials: KG
authors.lastname: Sylvester
authors.affiliation: Laboratory of Liver Regeneration, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Geuman-dong, Duckjin-gu, Jeonju, 561-712, South Korea; Department of Surgery, Chonbuk National University Medical School, 634-18 Geuman-dong, Duckjin-gu, Jeonju, 516-712, South Korea. Electronic address: surgeon@jbnu.ac.kr.
authors.forename: Yeon Jun
authors.initials: YJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D008115:Liver Regeneration / Q000502:physiology*; D008297:Male; D051379:Mice; D023421:Models, Animal; D000072340:NIMA-Interacting Peptidylprolyl Isomerase / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse
keywords: 3, 5-Diethoxycarbonyl-1; 4-Dihydrocollidine; Hepatic progenitor cells; Liver injury; Oval cells; Peptidyl-prolyl isomerase Pin1