Chronic blockade of the (pro)renin receptor ameliorates the kidney damage in the non-clipped kidney of Goldblatt hypertension

Kiyomoto, Hideyasu; Moriwaki, Kumiko

doi:10.1038/hr.2010.253

Cited by 4 publications

(1 citation statement)

References 33 publications

(35 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These controversies may be explained by the prorenin-renin ratio since the decoys were effective in high prorenin/low renin models (1,11), and/or by the length of treatment based on the observation that renoprotective effects were able to be observed after 12 weeks even in a high renin Goldblatt model (12,13). …”

Section: Introductionmentioning

confidence: 99%

The (pro)renin receptor mediates constitutive PLZF-independent pro-proliferative effects which are inhibited by bafilomycin but not genistein

Kirsch

Schrezenmeier

Klare

et al. 2014

International Journal of Molecular Medicine

View full text Add to dashboard Cite

The (pro)renin receptor [(P)RR] is crucial for cardio-renal pathophysiology. The distinct molecular mechanisms of this receptor are still incompletely understood. The (P)RR is able to interact with different signalling proteins such as promyelocytic leukemia zinc finger protein (PLZF) and Wnt receptors. Moreover, domains of the (P)RR are essential for V-ATPase activity. V-ATPase- and Wnt-mediated effects imply constitutive, i.e., (pro)renin-independent functions of the (P)RR. Regarding ligand-dependent (P)RR signalling, the role of prorenin glycosylation is currently unknown. Therefore, the aim of this study was to analyse the contribution of constitutive (P)RR activity to its cellular effects and the relevance of prorenin glycosylation on its ligand activity. We were able to demonstrate that high glucose induces (P)RR signal transduction whereas deglycosylation of prorenin abolishes its intrinsic activity in neuronal and epithelial cells. By using siRNA against (P)RR or PLZF as well as the PLZF translocation blocker genistein and the specific V-ATPase inhibitor bafilomycin, we were able to dissect three distinct sub-pathways downstream of the (P)RR. The V-ATPase function is ligand-independently associated with strong pro-proliferative effects whereas prorenin causes moderate proliferation in vitro. In contrast, PLZF per se [i.e., in the absence of (pro)renin] does not interfere with cell number.

show abstract