Cellular retinol-binding protein-1 expression and modulation during in vivo and in vitro myofibroblastic differentiation of rat hepatic stellate cells and portal fibroblasts.
Cellular retinol-binding protein-1 (CRBP-1) is involved in vitamin A metabolism because it mediates both retinol esterification to retinyl esters and retinol oxidation to retinal and retinoic acid. CRBP-1 is highly expressed in the liver, particularly in hepatic stellate cells (HSC). In this study, we investigated the liver expression of CRBP-1 during experimental fibrogenesis. We also studied the regulation of CRBP-1 expression in cultured HSC and portal fibroblasts, two fibroblastic cell types involved in liver fibrogenesis. Fibrosis was induced in rats by carbon tetrachloride (CCl(4)) or bile duct ligation. Immunohistochemical staining was performed for CRBP-1 and alpha-smooth muscle (SM) actin, an activation marker of fibrogenic cells. CRBP-1 and alpha-SM actin expression was studied by Western blotting and/or Northern blot in primary cultures of HSC isolated by conventional methods and in portal fibroblasts that were obtained by outgrowth from the biliary tree after enzymatic digestion. In normal liver, contrary to HSC, portal fibroblasts did not express CRBP-1. After CCl(4) injury, CRBP-1 expression was maintained in myofibroblastic alpha-SM actin-positive HSC. After bile duct ligation, portal fibroblasts (which proliferated around ductular structures) acquired expression of both CRBP-1 and alpha-SM actin. During HSC activation in culture, CRBP-1 expression gradually increased until Day 5 when alpha-SM actin expression was obvious. Cultured portal fibroblasts developed both CRBP-1 and alpha-SM actin expression. In both cell populations, transforming growth factor-beta 1 treatment increased CRBP-1 expression. Thus, in normal liver, CRBP-1 expression was different among fibroblastic cells, a finding that adds to the concept of heterogeneity of liver fibrogenic cells. Furthermore, during myofibroblastic differentiation, HSC that lost their stores of retinol maintained a high level of CRBP-1 expression, whereas portal fibroblasts acquired CRBP1 expression. Together, these data suggest a correlation between CRBP-1 expression and myofibroblastic differentiation.
Uchio
Kozue
K
Groupe de Recherches pour l'Etude du Foie, Université Victor Segalen Bordeaux 2, Bordeaux, France.
Tuchweber
Beatriz
B
Manabe
Noboru
N
Gabbiani
Giulio
G
Rosenbaum
Jean
J
Desmoulière
Alexis
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007124:Immunoenzyme Techniques; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011168:Portal System / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012177:Retinol-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D054840:Retinol-Binding Proteins, Cellular
D000199:Actins; D012333:RNA, Messenger; C518458:Rbp1 protein, rat; D012177:Retinol-Binding Proteins; D054840:Retinol-Binding Proteins, Cellular