title: Expression pattern of thymosin beta 4 in the adult human liver.
abstract: Thymosin beta-4 (Tβ4) is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tβ4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tβ4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tβ4 commercial antibody. Tβ4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tβ4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1). At higher power, Tβ4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tβ4. The current work first evidences a strong diffuse expression of Tβ4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tβ4 in adulthood. Moreover, Tβ4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tβ4.
authors.affiliation: Dipartimento di Citomorfologia, Divisione di Anatomia Patologica, Università di Cagliari, Italy. sonianemolato@libero.it
authors.forename: S
authors.initials: S
authors.lastname: Nemolato
authors.forename: P
authors.initials: P
authors.lastname: Van Eyken
authors.forename: T
authors.initials: T
authors.lastname: Cabras
authors.forename: F
authors.initials: F
authors.lastname: Cau
authors.forename: M U
authors.initials: MU
authors.lastname: Fanari
authors.forename: A
authors.initials: A
authors.lastname: Locci
authors.forename: D
authors.initials: D
authors.lastname: Fanni
authors.forename: C
authors.initials: C
authors.lastname: Gerosa
authors.forename: I
authors.initials: I
authors.lastname: Messana
authors.forename: M
authors.initials: M
authors.lastname: Castagnola
authors.forename: G
authors.initials: G
authors.lastname: Faa
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013947:Thymosin / Q000096:biosynthesis*; D000099201:Thymosin beta(4)
chemical_list: D013947:Thymosin; D000099201:Thymosin beta(4)
references.citation: Biochim Biophys Acta. 2001 Nov 7;1568(1):60-6
references.pmid: 11731086
references.citation: Ann N Y Acad Sci. 2007 Sep;1112:425-34
references.pmid: 17947593
references.citation: Peptides. 2009 Oct;30(10):1822-32
references.pmid: 19631707
references.citation: Proc Natl Acad Sci U S A. 1992 May 15;89(10):4678-82
references.pmid: 1584803
references.citation: Ann N Y Acad Sci. 2007 Sep;1112:21-37
references.pmid: 17468232
references.citation: World J Surg. 2005 Mar;29(3):264-70
references.pmid: 15706436
references.citation: Immunopharmacology. 1984 Feb;7(1):9-16
references.pmid: 6715146
references.citation: Eur J Histochem. 2010 Feb 16;54(1):e3
references.pmid: 20353910
references.citation: Prog Histochem Cytochem. 2007;41(4):201-66
references.pmid: 17368308
references.citation: Biochemistry. 1992 Jul 14;31(27):6179-85
references.pmid: 1627561
references.citation: Basic Res Cardiol. 2008 May;103(3):203-15
references.pmid: 17999026
references.citation: PLoS One. 2010 Feb 09;5(2):e9111
references.pmid: 20161756
references.citation: Proc Natl Acad Sci U S A. 1982 Jul;79(13):4006-9
references.pmid: 6955787
references.citation: Int J Biochem Cell Biol. 2001 Mar;33(3):205-20
references.pmid: 11311852
references.citation: Int Immunopharmacol. 2003 Aug;3(8):1225-33
references.pmid: 12860178
references.citation: Ann N Y Acad Sci. 2007 Sep;1112:154-60
references.pmid: 17584975
references.citation: Proc Natl Acad Sci U S A. 1990 Apr;87(7):2536-40
references.pmid: 2320573
references.citation: Nature. 2004 Nov 25;432(7016):466-72
references.pmid: 15565145
references.citation: PLoS One. 2009;4(4):e5109
references.pmid: 19337364
references.citation: J Invest Dermatol. 1999 Sep;113(3):364-8
references.pmid: 10469335
references.citation: Nat Med. 1999 Dec;5(12):1424-7
references.pmid: 10581087
references.citation: Proc Natl Acad Sci U S A. 1965 Apr;53:812-7
references.pmid: 14324539
references.citation: J Biol Chem. 1996 Apr 19;271(16):9223-30
references.pmid: 8621581
references.citation: J Sep Sci. 2009 Jan;32(1):57-63
references.pmid: 19035385
references.citation: Cell Biol Int. 2006 Jun;30(6):514-20
references.pmid: 16677835
references.citation: FASEB J. 2002 May;16(7):691-6
references.pmid: 11978733
references.citation: Cell Motil Cytoskeleton. 2009 Oct;66(10):839-51
references.pmid: 19405116
references.citation: Ann N Y Acad Sci. 2007 Sep;1112:458-65
references.pmid: 17600285
references.citation: Hepatology. 1995 Jun;21(6):1658-67
references.pmid: 7768512
references.citation: Ann N Y Acad Sci. 2007 Sep;1112:418-24
references.pmid: 17495244
references.citation: Biochem J. 1998 Jan 1;329 ( Pt 1):17-35
references.pmid: 9405271
references.citation: Blood. 1990 Sep 1;76(5):977-84
references.pmid: 2393720
references.citation: Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2388-95
references.pmid: 15980226