Lecithin: retinol acyltransferase protein is distributed in both hepatic stellate cells and endothelial cells of normal rodent and human liver

Abstract

Evidence has been accumulated that LRAT might serve as an excellent alternative HSC marker for future structural and functional studies. Furthermore, the presence of LRAT in endothelial cells might suggest a currently unknown function of this enzyme in liver endothelial biology.

Multiple cytochromeP-450 genes are concomitantly regulated by vitamin A under steady-state conditions and by retinoic acid during hepatic first-pass metabolism

“…As a positive marker for nonparenchymal cells, an ␣-SMA riboprobe was used; this probe hybridized in the smooth muscle cells (Fig. 6C, white arrows), consistent with a previous report (29).…”

“…Previously, we showed (36) that CYP2C22 is synthesized in the hepatocytes and that its mRNA transcript is detectable in the hepatocytes of vitamin A-adequate adult rats and increased in those cells when the rats are treated with RA. LRAT, on the other hand, is expressed in stellate cells as well as endothelial cells of the adult rat liver (29). As CYP26A1 may be the major RA hydroxylase activity enzyme in the liver (53), we examined its localization by in situ hybridization in the liver of vitamin A-deficient and vitamin A-adequate rats treated with exogenous RA.…”

Genetic dissection of retinoid esterification and accumulation in the liver and adipose tissue

“…Because DGAT1 is highly expressed in the liver, this raises a question as to whether DGAT1 might also act as an ARAT in the liver. Moreover, DGAT1 is expressed both in hepatocytes and in hepatic stellate cells ( 44 ), the cellular site in the liver where REs are stored and where LRAT is primarily expressed ( 48 ). Even though our earlier studies of Lrat Ϫ / Ϫ mice established that these mutant mice have very low levels of hepatic REs (<0.1% of matched WT levels) suggesting that LRAT is responsible for the preponderance of hepatic RE synthesis when mice are maintained on a standard chow diet ( 17 ), the literature suggests a role for an ARAT in hepatic RE formation.…”

Human hepatic stellate cell isolation and characterization

“…LRAT-positive staining was demonstrated in the space of Disse of normal human liver, and was suggested to be recognized as a quiescent HSC marker in human tissue [73]. LRAT?/ CRBP-1?…”

“…In normal and pathological adult human livers, positive immunostaining of a-SMA was identified in fat-droplet-containing HSCs, and increased cell number and intensity of the staining signal was observed in the specimens with chronic liver disease [66,68,72]. Some studies reported no a-SMA immunoreactivity detected in normal human liver [42,73]. Expression of vimentin, vinculin, procollagens I, III, collagen IV, V, laminin, and fibronectin are identified in human HSCs [23,39,64,70].…”