Alpini G, Glaser S, Robertson W, Phinizy J L, Rodgers R E, Caligiuri A, LeSage G
Department of Internal Medicine, Scott and White Hospital, Temple, Texas, USA.
Am J Physiol. 1997 Aug;273(2 Pt 1):G518-29. doi: 10.1152/ajpgi.1997.273.2.G518.
Accumulation of bile acids (BA) and cholangiocyte proliferation occur in cholestasis, but BA effects on the proliferative and secretory capacity of cholangiocytes are undefined. Cholangiocyte proliferation coupled with increased expression of H3 histone and secretin receptor (SR) genes and secretin-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) levels is limited to large cholangiocytes. We isolated pooled small and large cholangiocytes and studied the effect of taurocholic (TC) and taurolithocholic (TLC) acids on proliferation, by measurement of H3 histone gene expression, and secretion, by measurement of SR gene expression, cAMP levels, and Cl-/HCO3- exchanger activity. In pooled cholangiocytes, TC and TLC increased H3 histone (12-fold) and SR (3-fold) gene expression and both spontaneous (1.4-fold) and secretin-induced (4-fold) cAMP response. TC and TLC increased H3 histone (10-fold) and SR (2-fold) gene expression and secretin-induced cAMP response and Cl-/HCO3- exchanger activity (3-fold) only in large cholangiocytes. In large cholangiocytes, BA may have a signaling function in the modulation of ductal secretion.
胆汁淤积时会出现胆汁酸（BA）蓄积和胆管细胞增殖，但BA对胆管细胞增殖和分泌能力的影响尚不清楚。胆管细胞增殖与H3组蛋白和促胰液素受体（SR）基因表达增加以及促胰液素刺激的3',5'-环磷酸腺苷（cAMP）水平升高相关，且仅限于大胆管细胞。我们分离了混合的小胆管细胞和大胆管细胞，并通过测量H3组蛋白基因表达来研究牛磺胆酸（TC）和牛磺石胆酸（TLC）对增殖的影响，通过测量SR基因表达、cAMP水平和Cl⁻/HCO₃⁻交换体活性来研究其对分泌的影响。在混合胆管细胞中，TC和TLC增加了H3组蛋白（12倍）和SR（3倍）基因表达以及自发（1.4倍）和促胰液素诱导（4倍）的cAMP反应。TC和TLC仅在大胆管细胞中增加了H3组蛋白（10倍）和SR（2倍）基因表达、促胰液素诱导的cAMP反应以及Cl⁻/HCO₃⁻交换体活性（3倍）。在大胆管细胞中，BA可能在调节胆管分泌中具有信号传导功能。
