Staels B, Auwerx J
Department of Developmental Biology, Gasthuisberg, Katholieke Universiteit Leuven, Belgium.
Development. 1992 Aug;115(4):1035-43. doi: 10.1242/dev.115.4.1035.
Liver lipoprotein lipase (LPL) and alpha-fetoprotein (AFP) gene expression show similar developmental patterns. Both mRNAs are abundantly expressed in neonatal rat liver and gradually disappear upon ageing. Treatment with fibric acid derivatives, such as fenofibrate, not only delays the developmental extinction of the LPL gene, but also increases LPL mRNA levels in neonatal rat liver. Similarly, the developmental extinction of the AFP gene in the liver is clearly delayed after fenofibrate. In adult rat liver, fibric acid derivatives transcriptionally reinduce a mRNA with similar size as LPL, but no effect on AFP mRNA was detected. Sequence comparison of clones isolated from a fenofibrate-induced cDNA library demonstrates that the fenofibrate-(re)induced mRNA in adult rat liver is encoding for LPL. The induction of LPL after fenofibrate is tissue-specific, since heart and adipose tissue LPL mRNA levels remain unchanged. In conclusion, fibric acid derivatives modulate developmental expression patterns in rat liver, and may selectively reinduce the expression of extinct genes in adult rat liver.
肝脏脂蛋白脂肪酶（LPL）和甲胎蛋白（AFP）基因表达呈现相似的发育模式。两种mRNA在新生大鼠肝脏中均大量表达，并随年龄增长逐渐消失。用纤维酸衍生物（如非诺贝特）处理，不仅会延迟LPL基因的发育性消失，还会增加新生大鼠肝脏中LPL mRNA的水平。同样，非诺贝特处理后，肝脏中AFP基因的发育性消失也明显延迟。在成年大鼠肝脏中，纤维酸衍生物转录性地重新诱导出一种大小与LPL相似的mRNA，但未检测到对AFP mRNA有影响。从非诺贝特诱导的cDNA文库中分离出的克隆进行序列比较表明，成年大鼠肝脏中由非诺贝特（重新）诱导的mRNA编码的是LPL。非诺贝特处理后LPL的诱导具有组织特异性，因为心脏和脂肪组织中LPL mRNA水平保持不变。总之，纤维酸衍生物可调节大鼠肝脏中的发育表达模式，并可能选择性地重新诱导成年大鼠肝脏中已消失基因的表达。
