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 characterised 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 relationship to stellate cell activation remain unclear.
Methods: With use of cultured PSCs, an attempt was made to characterise the function of albumin endogenously expressed in stellate cells.
Results: Albumin is endogenously expressed in quiescent PSCs, localised 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 transforming growth factor β (TGFβ). 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 small interfering RNA (siRNA) abolishes retinol-induced effects.
Conclusions: The 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.
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Funding This work was supported by the 21C Frontier Functional Human Genome Project (grants FG-08-21-16) from the Ministry of Science and Technology of Korea.
Competing interests None.
Provenance and Peer review Not commissioned; externally peer reviewed.
See Commentary, p 1319
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