Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor
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Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor. / Bisgaard, Hanne Cathrine; Holmskov, Uffe; Santoni-Rugiu, Eric; Nagy, Peter; Nielsen, Ole; Ott, Peter; Hage, Ester; Dalhoff, Kim; Rasmussen, Lene Juel; Tygstrup, Niels.
I: American Journal of Pathology, Bind 161, Nr. 4, 64395, 2002, s. 1187-1198.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Heterogeneity of ductular reactions in adult rat and human liver revealed by novel expression of deleted in malignant brain tumor
AU - Bisgaard, Hanne Cathrine
AU - Holmskov, Uffe
AU - Santoni-Rugiu, Eric
AU - Nagy, Peter
AU - Nielsen, Ole
AU - Ott, Peter
AU - Hage, Ester
AU - Dalhoff, Kim
AU - Rasmussen, Lene Juel
AU - Tygstrup, Niels
PY - 2002
Y1 - 2002
N2 - The regenerative capacity of mammalian adult liver reflects the ability of a number of cell populations within the hepatic lineage to take action. Limited information is available regarding factors and mechanisms that determine the specific lineage level at which liver cells contribute to liver repair as well as the fate of their progeny in the hostile environment created by liver injury. In the present study, we attempted to identify novel molecules preferentially involved in liver regeneration by recruitment of transitamplifying, ductular (oval) cell populations. With a subtractive cDNA library screening approach, we identified 48 enriched, nonredundant gene products associated with liver injury and oval cell proliferation in the adult rat liver. Of these, only two, namely α-fetoprotein and a novel transcript with high homology to human DMBT1 (deleted in malignant brain tumor 1), were specifically associated with the emergence of ductular (oval) cell populations in injured liver. Subsequent cloning and characterization of the rat DMBT1 homologue revealed a highly inducible expression in ductular reactions composed of transitamplifying ductular (oval) cells, but not in ductular reactions after ligation of the common bile duct. In human liver diseases, DMBT1 was expressed in ductular reactions after infection with hepatitis B and acetaminophen intoxication, but not in primary primary biliary cirrhosis, primary sclerosing cholangitis, and obstruction of the large bile duct. The expression heterogeneity in ductular reactions and multiple functions of DMBT1 homologues point to intriguing roles in regulating not only tissue repair but also fate decision and differentiation paths of specific cell populations in the hepatic lineage.
AB - The regenerative capacity of mammalian adult liver reflects the ability of a number of cell populations within the hepatic lineage to take action. Limited information is available regarding factors and mechanisms that determine the specific lineage level at which liver cells contribute to liver repair as well as the fate of their progeny in the hostile environment created by liver injury. In the present study, we attempted to identify novel molecules preferentially involved in liver regeneration by recruitment of transitamplifying, ductular (oval) cell populations. With a subtractive cDNA library screening approach, we identified 48 enriched, nonredundant gene products associated with liver injury and oval cell proliferation in the adult rat liver. Of these, only two, namely α-fetoprotein and a novel transcript with high homology to human DMBT1 (deleted in malignant brain tumor 1), were specifically associated with the emergence of ductular (oval) cell populations in injured liver. Subsequent cloning and characterization of the rat DMBT1 homologue revealed a highly inducible expression in ductular reactions composed of transitamplifying ductular (oval) cells, but not in ductular reactions after ligation of the common bile duct. In human liver diseases, DMBT1 was expressed in ductular reactions after infection with hepatitis B and acetaminophen intoxication, but not in primary primary biliary cirrhosis, primary sclerosing cholangitis, and obstruction of the large bile duct. The expression heterogeneity in ductular reactions and multiple functions of DMBT1 homologues point to intriguing roles in regulating not only tissue repair but also fate decision and differentiation paths of specific cell populations in the hepatic lineage.
UR - http://www.scopus.com/inward/record.url?scp=0036792510&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64395-7
DO - 10.1016/S0002-9440(10)64395-7
M3 - Journal article
C2 - 12368192
AN - SCOPUS:0036792510
VL - 161
SP - 1187
EP - 1198
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 4
M1 - 64395
ER -
ID: 257667520