Induction of LRF-1/ATF3 by Vasopressin in Hepatocytes: Role of MAP Kinases
Cellular Physiology and Biochemistry
Background/Aims: Liver regeneration factor 1 (LRF-1/ATF3) is an early response gene which is rapidly induced upon partial hepatectomy in rats, and by growth factors and G protein-coupled receptor (GPCR) agonists in cultured rat hepatocytes. The aim of the present study was to examine the mechanisms involved in induction of LRF-1/ATF3 by the GPCR agonist vasopressin. Methods: Primary cultures of rat hepatocytes were treated with vasopressin, TPA, and the Ca 2+ -elevating agents thapsigargin and
... s thapsigargin and A23187. LRF-1/ATF3 mRNA and protein were measured by Northern blot analysis or RT-PCR and immunoblotting. Signalling pathways were examined by immunoblots and kinase assays. Results: While elevation of intracellular calcium induced LRF-1/ATF3 expression, treatment with TPA did not. Inhibition of phospholipase C, protein kinase C, or pretreatment with calcium chelators did not affect vasopressin-induced expression of LRF-1/ATF3. Inhibition of each of the MAP kinases ERK1/2, JNK or p38 did not affect vasopressin-induced LRF-1/ATF3 expression. Combined inhibition of JNK and p38, and of ERK1/2 and either JNK or p38 suppressed vasopressininduced expression of LRF-1/ATF3. Conclusion: Vasopressin induces LRF-1/ATF3 expression by mechanisms that differ from those activated by Ca 2+elevating agents. The results suggest that partly redundant, complex MAP kinase networks are involved in induction of LRF-1/ATF3 by vasopressin in hepatocytes.