The effect of retinol on Ito cell proliferation in vitro

Hepatic sinusoidal fat-storing Ito cells are felt to represent the primary storage site for hepatic vitamin A and may be important collagen-producing effector cells during hepatic fibrogenesis. The cirrhotic liver generally has a decreased vitamin A content with increased numbers of "transitional" myofibroblasts adjacent to developing fibrous bands. It has been suggested that Ito cells "transform" into these myofibroblasts. The in vivo loss of Ito cell vitamin A can be simulated in vitro as Ito cells spontaneously lose their vitamin A lipid droplets during primary culture. The current study evaluated Ito cell proliferation in vitro with respect to vitamin A content and the extracellular collagen matrix. The cells were grown on a Type I or Type IV collagen matrix to simulate the types of collagens presumed to be present in the space of Disse. Initially it was observed that freshly isolated Ito cells begin to proliferate several days after isolation coincident with the decline of the vitamin A lipid droplets and a decrease in cellular retinyl palmitate. The proliferation rate for passaged Ito cells was similar on either matrix (on Type I collagen: T 1/2 = 2.2 +/- 1.1 days, n = 16; on Type IV collagen: T 1/2 = 3.3 +/- 1.4 days, n = 4; p less than 0.11). This proliferation rate remained constant through Cell Generation 16 and was similar to the rate for primary Ito cells in culture. To evaluate the possibility that primary Ito cell proliferation is causally related to the loss of vitamin A, Ito cells were re-exposed to an increased concentration of retinol in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)