title: Continuous high expression of XBP1 and GRP78 is important for the survival of bone marrow cells in CCl4-treated cirrhotic liver.
abstract: We have previously shown that infusion of bone marrow cells (BMC) improves CCl(4)-induced cirrhosis. However, it is unclear why the injected BMC are resistant to CCl(4) damage and subsequently improve the local microenvironment in damaged liver. To analyze the cellular phenomena involved in this process, we studied the damaged liver using electron microscopy. We found that CCl(4) caused rough endoplasmic reticula to swell in hepatocytes. To analyze the gene expression patterns associated with this process, we conducted PCR-selected suppressive subtractive hybridization. We found that expression levels of HSP84, HSP40, and XBP1 differed markedly between control liver and liver infused with BMC. Immunohistochemical staining revealed that expression levels of HSP84 and HSP40 were markedly higher in the early phase of differentiation immediately after BMC infusion, but decreased over time. XBP1 expression remained high during the late phase, and GRP78 expression increased with XBP1 activation. We also found that GFP-positive BMC expressed XBP1 and GRP78. XBP1 and GRP78 are associated with ER stress. Thus, continuous high XBP1 and GRP78 expression might be essential for the survival and proliferation of BMC in a CCl(4)-induced persistent liver damage environment.
authors.affiliation: Department of Gastroenterology & Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Marumoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Terai
authors.forename: Yohei
authors.initials: Y
authors.lastname: Urata
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Mizunaga
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Haiyan
authors.initials: H
authors.lastname: Jin
authors.forename: Koichi
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Murata
authors.forename: Koh
authors.initials: K
authors.lastname: Shinoda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishina
authors.forename: Isao
authors.initials: I
authors.lastname: Sakaida
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D002251:Carbon Tetrachloride; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D000091342:Endoplasmic Reticulum Chaperone BiP; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D050956:HSP40 Heat-Shock Proteins / Q000096:biosynthesis; D018841:HSP90 Heat-Shock Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D007150:Immunohistochemistry; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D018832:Molecular Chaperones / Q000096:biosynthesis* / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; C494641:Dnajb1 protein, mouse; D000091342:Endoplasmic Reticulum Chaperone BiP; D050956:HSP40 Heat-Shock Proteins; C488983:HSP84 protein, mouse; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605544:Xbp1 protein, mouse; D003577:Cytochrome P-450 Enzyme System; D002251:Carbon Tetrachloride