Conclusion
Manipulation of cholangiocyte VEGF expression by bile acids may be important in preventing the impairment of cholangiocyte proliferation by exogenous agents.
Methods
Normal and BDL rats (immediately after surgery) were fed 1% TC or control diet in the absence/presence of daily IP injections of CAPE (10 mg/Kg BW). One week later, we evaluated: (i) cholangiocyte apoptosis, proliferation and ductal mass in liver sections; (ii) functional activity by measuring secretin-stimulated bile and bicarbonate secretion; and (iii) VEGF-A/C and VEGFR-2/R-3 expression in liver sections. In vitro, BDL cholangiocytes were exposed to CAPE (40 microM) in the absence/presence of TC (40 microM) with and without pretreatment with VEGF receptor inhibitors before evaluating cholangiocyte apoptosis and proliferation.
Results
Chronic CAPE administration to BDL rats increased cholangiocyte apoptosis and decreased ductal mass. This effect was associated with reduced expression of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3. In vivo, TC feeding partly prevented CAPE-induced changes in cholangiocyte apoptosis and growth and loss of ductal secretion. The protective effect of TC was associated with enhanced VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3. In vitro, TC partially prevented CAPE-induced increases in apoptosis and decreases in cholangiocyte proliferation. These changes were reversed by pretreatment with VEGF-receptor inhibitors.