Objective: Quiescent pancreatic stellate cells (PSCs) store vitamin A as cytoplasmic lipid droplets, and when activated by profibrogenic stimuli, they transform into myofibroblast-like cells characterized by the loss of vitamin A droplets. Activation of stellate cells is central to fibrogenesis, but the mechanism for the formation of vitamin A droplets and its relation to stellate cell activation remain unclear.
Design: With use of cultured pancreatic stellate cells, we sought to characterize the function of albumin endogenously expressed in stellate cells.
Results: Albumin is endogenously expressed in quiescent PSCs, localized in cytoplasmic lipid droplets, and its levels are markedly reduced after stellate cell activation. Continuous albumin expression in stellate cells is sufficient to maintain their fat-storing phenotype even after cell passages and renders cells resistant to the activating effects of TGF-β. Forced expression of albumin in PSCs after passage 2 (activated PSCs) induced the re-appearance of lipid droplets and phenotypic changes, which were previously reported with retinol treatment. Retinol increases albumin synthesis in activated PSCs and the suppression of albumin expression using siRNA abolishes retinol-induced effects.
Conclusions: Our data demonstrate a novel role for albumin in the formation of cytoplasmic vitamin A lipid droplets in stellate cells, and suggest that albumin may have a direct influence on stellate cell activation.