TY - JOUR
T1 - Nephronectin is upregulated in acute and chronic hepatitis and aggravates liver injury by recruiting CD4 positive cells
AU - Inagaki, Fuyuki F.
AU - Tanaka, Minoru
AU - Inagaki, Natsuko F.
AU - Yagai, Tomoki
AU - Sato, Yuya
AU - Sekiguchi, Kiyotoshi
AU - Oyaizu, Naoki
AU - Kokudo, Norihiro
AU - Miyajima, Atsushi
N1 - Funding Information:
We would like to thank Dr. Tohru Ito for providing us with the pLIVE-SEAP vector and Ms. Naoko Miyata for the excellent cell sorting. This work was supported in part by research grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan , Ministry of Health, Labour, and Welfare of Japan , the CREST program of the Japan Science and Technology Agency , and the Takeda Science Foundation .
PY - 2013/1/11
Y1 - 2013/1/11
N2 - 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.
AB - 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.
KW - Acute hepatitis
KW - Chronic hepatitis
KW - Liver
KW - Nephronectin
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U2 - 10.1016/j.bbrc.2012.11.076
DO - 10.1016/j.bbrc.2012.11.076
M3 - Article
C2 - 23206711
AN - SCOPUS:84872285905
VL - 430
SP - 751
EP - 756
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -
