PLZF and the (pro)renin receptor.
For many years, angiotensin II with its respective receptors was considered to be the only effector molecule within the renin-angiotensin system. Nevertheless, several studies indicated that renin (the enzyme catalyzing the generation of angiotensin I) and its enzymatically inactive precursor prorenin may have an angiotensin-II-independent (patho)physiological significance. In 2002, a specific (pro)renin receptor ((P)RR)) which increases the enzymatic activity of its ligands and induces an intrinsic activity upon ligand binding has been published. Recently, our group has demonstrated a novel (P)RR signal transduction pathway involving direct protein-protein interaction between the (P)RR and the transcription factor promyelocytic zinc finger protein (PLZF) and the nuclear translocation of PLZF upon renin stimulation. Downstream effects of (P)RR activation by renin included repression of the (P)RR itself and induction of the p85alpha subunit of the phosphatidylinositol-3 kinase (PI3K-p85alpha) as well as an increase in proliferation and a decrease in apoptotic activity. Various animal models demonstrated that inhibition of prorenin binding to the (P)RR can prevent or even abolish the development of cardiac fibrosis and diabetic nephropathy via angiotensin-II-independent mechanisms. Additional studies that verify these remarkable findings are needed. Moreover, the potency of aliskiren (the first orally active renin inhibitor in the market) to interfere with a putatively detrimental binding of (pro)renin to the (P)RR is of particular interest and has to be elucidated.
Schefe
Jan H
JH
Center for Cardiovascular Research (CCR), Institute of Pharmacology, Charité-Universitätsmedizin Berlin, Hessische Strasse 3-4, Berlin, Germany.
Unger
Thomas
T
Funke-Kaiser
Heiko
H
D000818:Animals; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors
D051741:Kruppel-Like Transcription Factors; D011956:Receptors, Cell Surface; D000093342:Prorenin Receptor; D000092502:Renin Inhibitors