Rat hepatic stellate cells acquire retinoid responsiveness after activation in vitro by post-transcriptional regulation of retinoic acid receptor alpha gene expression.
Activation of hepatic stellate cells (HSCs) is a key process in liver fibrogenesis and retinoid loss is a remarkable feature of activated HSCs. However, roles of retinoids in liver fibrogenesis are obscure. We show that mRNA levels of RARalpha, beta and gamma were decreased during rat HSC activation in vitro. However, protein levels of RARalpha and beta were increased during HSC activation. A retinoic acid response element-containing luciferase assay indicated that HSCs became responsive to retinoids only after activation in vitro and that this response was mediated by, at least in part, RARalpha subtype. Immunocytochemical analysis showed that RARalpha proteins were mainly distributed in cytosol as many spots. All-trans retinoic acid treatment strongly lowered the cytosolic RARalpha protein levels. These results indicate that rat HSCs become retinoid responsive after activation in vitro, through post-transcriptional up-regulation of RARalpha gene expression.
Mezaki
Yoshihiro
Y
Department of Cell Biology and Histology, Akita University School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan.
Yoshikawa
Kiwamu
K
Yamaguchi
Noriko
N
Miura
Mitsutaka
M
Imai
Katsuyuki
K
Kato
Shigeaki
S
Senoo
Haruki
H
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids / Q000378:metabolism*; D012177:Retinol-Binding Proteins / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D014212:Tretinoin / Q000008:administration & dosage*
C000607073:Rara protein, rat; C518458:Rbp1 protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular; D014212:Tretinoin