Nephronectin is upregulated in acute and chronic hepatitis and aggravates liver injury by recruiting CD4 positive cells

Fuyuki F. Inagaki, Minoru Tanaka, Natsuko F. Inagaki, Tomoki Yagai, Yuya Sato, Kiyotoshi Sekiguchi, Naoki Oyaizu, Norihiro Kokudo, Atsushi Miyajima

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)751-756
Number of pages6
JournalBiochemical and biophysical research communications
Volume430
Issue number2
DOIs
Publication statusPublished - 2013 Jan 11
Externally publishedYes

Keywords

  • Acute hepatitis
  • Chronic hepatitis
  • Liver
  • Nephronectin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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