Involvement of (pro)renin receptor in the glomerular filtration barrier

(Pro)renin receptor-bound prorenin not only causes the generation of angiotensin II via the nonproteolytic activation of prorenin, it also activates the receptor’s own intracellular signaling pathways independent of the generated angiotensin II. Within the kidneys, the (pro)renin receptor is not only present in the glomerular mesangium, it is also abundant in podocytes, which play an important role in the maintenance of the glomerular filtration barrier. Recent in vivo studies have demonstrated that the overexpression of the (pro)renin receptor to a degree similar to that observed in hypertensive rat kidneys leads to slowly progressive nephropathy with proteinuria. In addition, the handle region peptide, which acts as a decoy peptide and competitively inhibits the binding of prorenin to the receptor, is more beneficial than an angiotensin-converting enzyme inhibitor with regard to alleviating proteinuria and glomerulosclerosis in experimental animal models of diabetes and essential hypertension. Thus, the (pro)renin receptor may be upregulated in podocytes under hypertensive conditions and may contribute to the breakdown of the glomerular filtration barrier

Ventilation of the abyssal Southern Ocean during the late Neogene: A new perspective from the subantarctic Pacific

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94630/1/palo1532.pd

Glacial‐interglacial variations in sediment organic carbon accumulation and benthic foraminiferal assemblages on the Bermuda Rise (ODP Site 1063) during MIS 13 to 10

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94866/1/palo1807.pd

New roles for renin and prorenin in heart failure and cardiorenal crosstalk

The renin-angiotensin-aldosterone-system (RAAS) plays a central role in the pathophysiology of heart failure and cardiorenal interaction. Drugs interfering in the RAAS form the pillars in treatment of heart failure and cardiorenal syndrome. Although RAAS inhibitors improve prognosis, heart failure–associated morbidity and mortality remain high, especially in the presence of kidney disease. The effect of RAAS blockade may be limited due to the loss of an inhibitory feedback of angiotensin II on renin production. The subsequent increase in prorenin and renin may activate several alternative pathways. These include the recently discovered (pro-) renin receptor, angiotensin II escape via chymase and cathepsin, and the formation of various angiotensin subforms upstream from the blockade, including angiotensin 1–7, angiotensin III, and angiotensin IV. Recently, the direct renin inhibitor aliskiren has been proven effective in reducing plasma renin activity (PRA) and appears to provide additional (tissue) RAAS blockade on top of angiotensin-converting enzyme and angiotensin receptor blockers, underscoring the important role of renin, even (or more so) under adequate RAAS blockade. Reducing PRA however occurs at the expense of an increase plasma renin concentration (PRC). PRC may exert direct effects independent of PRA through the recently discovered (pro-) renin receptor. Additional novel possibilities to interfere in the RAAS, for instance using vitamin D receptor activation, as well as the increased knowledge on alternative pathways, have revived the question on how ideal RAAS-guided therapy should be implemented. Renin and prorenin are pivotal since these are at the base of all of these pathways

(Pro)renin receptor: subcellular localizations and functions

Since its first report in 1996, the concept of the so-called (Pro)renin receptor ((P)RR/ATP6ap2) has dramactically evolved from a receptor mediating cellular effects of (pro)renin, to a protein with more basic and potentially essential intracellular functions. Among the arguments urging to reconsider the role of (P)RR was the observation that its localization appears mainly intracellular, although this does not preclude potential functions at the cell surface. However, despite about 10 years of research boosted by the generation of genetically modified animal models, the basic mechanisms of action of this protein at the cellular level remain elusive. This review aims at discussing the functions described for (P)RR in relation to its subcellular localization(s)

Physiology of the (pro)renin receptor: Wnt of change?

The (pro)renin receptor is a protein that binds prorenin and renin in tissues, leading to their activation and, at the same time, to the initiation of intracellular signaling. The activation of local renin-angiotensin systems may play an important role in tissue damage induced by cardiovascular diseases and diabetes. However, (pro)renin receptor is also called ATP6ap2 because it has been shown to be associated with vacuolar H(+)-ATPase involvement in vesicular acidification and signaling in cells. Notably, lack of the protein in vertebrates leads to developmental alterations and early embryonic lethality probably as a result of the recently discovered role of the (pro)renin receptor and the vacuolar H(+)-ATPase in Wnt signaling. This review summarizes the current findings about these two functions of (pro)renin receptor/ATP6ap2 pointing out the possible links between both