title: Nephronectin is upregulated in acute and chronic hepatitis and aggravates liver injury by recruiting CD4 positive cells.
abstract: Nephronectin (Npnt) is an extracellular matrix protein known to play a critical role in kidney development; however, its physiological role in the liver remains elusive. Here we show that Npnt expression is upregulated in mouse models of both acute and chronic hepatitis induced by Concanavalin A (Con A) and 3,5-diethocarbonyl-1,4-dihydrocollidine (DDC), respectively. In both models, Npnt was localized in inflammatory foci and was mainly secreted from mesenchymal cells and in part by cholangiocytes. Interestingly, ectopic expression of Npnt in hepatocytes induced the development of granuloma-like cell clusters mainly composed of CD4(+) T cells or NKT cells but did not induce apparent hepatitis. Furthermore, we found that Npnt exacerbated the Con A-induced acute hepatitis. These results indicate that Npnt plays an important role in the initiation of hepatitis by recruiting CD4(+) T cells or NKT cells into the foci of inflammation. In addition, we reveal that Npnt expression is also upregulated in human hepatitis. Therefore, Npnt may be a potential therapeutic target for acute and chronic hepatitis.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan. inagaki-tky@umin.ac.jp
authors.forename: Fuyuki F
authors.initials: FF
authors.lastname: Inagaki
authors.forename: Minoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Natsuko F
authors.initials: NF
authors.lastname: Inagaki
authors.forename: Tomoki
authors.initials: T
authors.lastname: Yagai
authors.forename: Yuya
authors.initials: Y
authors.lastname: Sato
authors.forename: Kiyotoshi
authors.initials: K
authors.lastname: Sekiguchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Oyaizu
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kokudo
authors.forename: Atsushi
authors.initials: A
authors.lastname: Miyajima
mesh_terms: D000208:Acute Disease; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D003208:Concanavalin A / Q000633:toxicity; D004195:Disease Models, Animal; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006099:Granuloma / Q000276:immunology / Q000473:pathology; D006505:Hepatitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D006521:Hepatitis, Chronic / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015854:Up-Regulation
chemical_list: D016326:Extracellular Matrix Proteins; C432915:nephronectin; D003208:Concanavalin A