The deleterious effect of hyperglycemia on the biology of the liver is supported by
clinical evidence. It can promote the development of fatty liver, liver fibrosis,
even liver cancer as complication of diabetes mellitus. As liver fibrosis is the consequence
of hepatic stellate cell (HSC) activation, the questions were addressed whether alterations
induced by high glucose concentration are directly related to TGFB1 effect, or other
mechanisms are activated. In order to obtain information on the response of HSC for
high glucose, LX-2 cells (an immortalized human HSC cell lineage) were cultured in
15.3 mM glucose containing medium for 21 days. The effect of glucose was compared
to that of TGFB1. Our data revealed that chronic exposure of high glucose concentration
initiated profound alteration of LX-2 cells and the effect is different from those
observed upon interaction with TGFB1. Whereas TGFB1 induced the production of extracellular
matrix proteins, high glucose exposure resulted in decreased MMP2 activity, retardation
of type I collagen in the endoplasmic reticulum, with decreased pS6 expression, pointing
to development of endoplasmic stress and sequestration of p21(CIP1/WAF1) in the cytoplasm
which can promote the proliferation of LX2 cells.
