title: Identification of a zinc finger homoeodomain enhancer protein after AT(2) receptor stimulation by differential mRNA display.
abstract: Using differential mRNA display, we isolated differentially expressed genes after stimulation of angiotensin II (Ang II) type 2 (AT(2)) receptors in PC12w cells. Among the polymerase chain reaction products isolated, we identified Zfhep, a zinc finger homoeodomain enhancer-binding protein and the angiotensin AT(2) receptor itself, both implicated in developmental processes. In the presence of epidermal growth factor (EGF) a concordant expression pattern of Zfhep and AT(2) mRNA was observed with marked downregulation 6 hours after stimulation with EGF+Ang II. In quiescent PC12w cells, Zfhep mRNA was time-dependently induced by Ang II (10(-7) mol/L) up to 3 hours, an effect that was blocked by the selective AT(2) antagonist PD123177 (10(-6) mol/L). We extended our studies on Zfhep mRNA expression to cells of vascular origin (coronary endothelial cells [CECs]), that express AT(1) and AT(2) receptors, and that respond differently to Ang II dependent on which receptor subtype is stimulated. In CECs, Zfhep mRNA expression was induced up to 3 hours after AT(2) stimulation. Interestingly, this Zfhep induction was observed only when the AT(1) receptor was blocked by using the selective AT(1) receptor antagonist, losartan (10(-5) mol/L), suggesting a negative-regulatory influence of AT(1) receptors on AT(2)-induced Zfhep mRNA induction. In conclusion, Zfhep not only represents a suitable marker for AT(2) receptor activation, but it may also link AT(2) signaling and downstream events involved in the proposed function of the AT(2) receptor in development and regeneration.
authors.affiliation: Department of Physiology, Medical College of Wisconsin, Milwaukee, USA. stoll@pharmakologie.uni-kiel.de
authors.forename: Monika
authors.initials: M
authors.lastname: Stoll
authors.forename: Alfred W A
authors.initials: AW
authors.lastname: Hahn
authors.forename: Uwe
authors.initials: U
authors.lastname: Jonas
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhao
authors.forename: Bernhard
authors.initials: B
authors.lastname: Schieffer
authors.forename: Jens W
authors.initials: JW
authors.lastname: Fischer
authors.forename: Thomas
authors.initials: T
authors.lastname: Unger
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D019439:Chromaffin Cells / Q000737:chemistry; D002999:Clone Cells; D003331:Coronary Vessels / Q000166:cytology; D004730:Endothelium, Vascular / Q000166:cytology; D020869:Gene Expression Profiling; D018398:Homeodomain Proteins / Q000302:isolation & purification*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017208:Rats, Wistar; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D014157:Transcription Factors / Q000302:isolation & purification*; D000071799:Zinc Finger E-box-Binding Homeobox 1; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D057911:Angiotensin Receptor Antagonists; D018398:Homeodomain Proteins; D012333:RNA, Messenger; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D014157:Transcription Factors; C000630720:ZEB1 protein, rat; D000071799:Zinc Finger E-box-Binding Homeobox 1; D019808:Losartan