Crosstalk between high-molecular-weight adiponectin and T-cadherin during liver fibrosis development in rats.
Adiponectin, a circulating adipocyte-derived secretory protein, reportedly plays an important role in liver fibrosis development, although the biological role of adiponectin in liver fibrogenesis is still controversial. Adiponectin is present in the serum as three oligometric complexes; namely, high-, middle-, and low-molecular weight (HMW, MMW, and LMW, respectively). Adiponectin exerts different biological activities in an oligomerization-dependent manner. The aim of our current study was to examine the alteration of each isoform of adiponectin and its receptors (AdipoR1, AdipoR2, and T-cadherin) during the choline-deficient L-amino acid-defined (CDAA) diet-induced rat liver fibrosis development. We also elucidated the methylation status of all receptors. The serum level of total adiponectin significantly increased during the liver fibrosis development. Among the three isoforms, only HMW adiponectin was significantly up-regulated whereas MMW and LMW were not. The expression of T-cadherin, which exclusively binds with HMW adiponectin, was significantly augmented as well. The AdipoR2 expression was markedly decreased and showed no marked difference from that of AdipoR1. No obvious methylation change was observed in all three receptors, suggesting that another mechanism is involved in the alteration of receptor gene expression. Collectively, since the specific ligand and receptor were augmented together, crosstalk between HMW adiponectin and T-cadherin may play an important role during liver fibrosis development in rats.
Asada
Kiyoshi
K
Third Department of Internal Medicine, Nara Medical University, Nara, Japan.
Yoshiji
Hitoshi
H
Noguchi
Ryuichi
R
Ikenaka
Yasuhide
Y
Kitade
Mitsuteru
M
Kaji
Kosuke
K
Yoshii
Junichi
J
Yanase
Koji
K
Namisaki
Tadashi
T
Yamazaki
Masaharu
M
Tsujimoto
Tatsuhiro
T
Akahane
Takemi
T
Uemura
Masahito
M
Fukui
Hiroshi
H
D052242:Adiponectin / Q000097:blood / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism*; D008297:Male; D008745:Methylation; D008970:Molecular Weight; D020836:Protein Structure, Quaternary; D051381:Rats; D011916:Rats, Inbred F344; D054419:Receptors, Adiponectin / Q000378:metabolism
D052242:Adiponectin; D015820:Cadherins; D054419:Receptors, Adiponectin